| Date | Panel | Item | Activity | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Infertility and Recurrent Pregnancy Loss v0.172 | SYCE1 | Zornitza Stark Marked gene: SYCE1 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Infertility and Recurrent Pregnancy Loss v0.172 | SYCE1 | Zornitza Stark Gene: syce1 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Infertility and Recurrent Pregnancy Loss v0.172 | SYCE1 | Zornitza Stark Classified gene: SYCE1 as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Infertility and Recurrent Pregnancy Loss v0.172 | SYCE1 | Zornitza Stark Gene: syce1 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Infertility and Recurrent Pregnancy Loss v0.82 | BCORL1 |
Jasmine Chew changed review comment from: i) PMID: 38342987- novel hemizygous nonsense variant (c.1564G > T:p.Glu522*) in a male patient with oligoasthenoteratozoospermia (OAT) from a Han Chinese family. Functional analysis showed that the variant produced a truncated protein with altered cellular localization and a dysfunctional interaction with SKP1 (S-phase kinase-associated protein 1). Also identified four hemizygous missense variants (c.2615T > G:p.Val872Gly, c.2669G > A:p.Arg890Gln, c.3164A > G:p.Asp1055Gly and c.3344C > T:p.Pro1115Leu) in subjects with both OAT (1 of 325, 0.31%) and NOA (4 of 355, 1.13%). They hypothesized that the BCORL1 (c.2615 T > G, c.2669G > A, c.3164A > G, c.3344C > T) missense mutations may have led to an accumulation of dysfunctional toxic proteins that resulted in a more severe male infertility phenotype in the patient (NOA). ii) PMID: 32376790- Hemizygous missense variant in a male patient with NOA without other diseases, which also found that the knockout of Bcorl1 in mice resulted in OAT with the abnormal brain development. It had not been previously linked to male infertility. This study demonstrates, for the first time, that loss of Bcorl1 causes spermatogenesis failure. iii) PMID: 39267058- hemizygous missense variant (p.Arg19Gln) in a infertile male with oliogasthenozoospermia, no functional data iv) PMID: 39189935- novel hemizygous missense variant (p.G1391R) and a recurrent variant (p.V872G) in BCORL1 from four OAT patients. Functional assays showed that the variants disturb the transcription of spermatogenetic genes such as SYCE1 and DAZL, impair the interaction with HDAC7, and cause epigenetic changes such as changes in level of histone modification with different extent, including the enhancement in acetylation of H3K14, and the reduction in acetylation of H4K5 and H4K8. Byrne et al. 2023- male fetus terminated at 22+3 GA due to abnormal renal morphology, Cleft upper lip, Median cleft palate, Ovotestis, enlarged hyroid, oral frenulae carrying hemizygous p.Tyr1692Ter called VUS- novel phenotype Sources: Literature; to: i) PMID: 38342987- novel hemizygous nonsense variant (c.1564G > T:p.Glu522*) in a male patient with oligoasthenoteratozoospermia (OAT) from a Han Chinese family. Functional analysis showed that the variant produced a truncated protein with altered cellular localization and a dysfunctional interaction with SKP1 (S-phase kinase-associated protein 1). Also identified four hemizygous missense variants (c.2615T > G:p.Val872Gly, c.2669G > A:p.Arg890Gln, c.3164A > G:p.Asp1055Gly and c.3344C > T:p.Pro1115Leu) in subjects with both OAT (1 of 325, 0.31%) and NOA (4 of 355, 1.13%). They hypothesized that the BCORL1 (c.2615 T > G, c.2669G > A, c.3164A > G, c.3344C > T) missense mutations may have led to an accumulation of dysfunctional toxic proteins that resulted in a more severe male infertility phenotype in the patient (NOA). ii) PMID: 32376790- Hemizygous missense variant in a male patient with NOA without other diseases, which also found that the knockout of Bcorl1 in mice resulted in OAT with the abnormal brain development. It had not been previously linked to male infertility. This study demonstrates, for the first time, that loss of Bcorl1 causes spermatogenesis failure. iii) PMID: 39267058- hemizygous missense variant (p.Arg19Gln) in a infertile male with oliogasthenozoospermia, no functional data iv) PMID: 39189935- novel hemizygous missense variant (p.G1391R) and a recurrent variant (p.V872G) in BCORL1 from four OAT patients. Functional assays showed that the variants disturb the transcription of spermatogenetic genes such as SYCE1 and DAZL, impair the interaction with HDAC7, and cause epigenetic changes such as changes in level of histone modification with different extent, including the enhancement in acetylation of H3K14, and the reduction in acetylation of H4K5 and H4K8. Sources: Literature |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Infertility and Recurrent Pregnancy Loss v0.82 | BCORL1 |
Jasmine Chew gene: BCORL1 was added gene: BCORL1 was added to Infertility and Pregnancy Loss. Sources: Literature Mode of inheritance for gene: BCORL1 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females Publications for gene: BCORL1 were set to 38342987; 32376790; 39267058; 39189935 Phenotypes for gene: BCORL1 were set to Spermatogenic failure Review for gene: BCORL1 was set to GREEN Added comment: i) PMID: 38342987- novel hemizygous nonsense variant (c.1564G > T:p.Glu522*) in a male patient with oligoasthenoteratozoospermia (OAT) from a Han Chinese family. Functional analysis showed that the variant produced a truncated protein with altered cellular localization and a dysfunctional interaction with SKP1 (S-phase kinase-associated protein 1). Also identified four hemizygous missense variants (c.2615T > G:p.Val872Gly, c.2669G > A:p.Arg890Gln, c.3164A > G:p.Asp1055Gly and c.3344C > T:p.Pro1115Leu) in subjects with both OAT (1 of 325, 0.31%) and NOA (4 of 355, 1.13%). They hypothesized that the BCORL1 (c.2615 T > G, c.2669G > A, c.3164A > G, c.3344C > T) missense mutations may have led to an accumulation of dysfunctional toxic proteins that resulted in a more severe male infertility phenotype in the patient (NOA). ii) PMID: 32376790- Hemizygous missense variant in a male patient with NOA without other diseases, which also found that the knockout of Bcorl1 in mice resulted in OAT with the abnormal brain development. It had not been previously linked to male infertility. This study demonstrates, for the first time, that loss of Bcorl1 causes spermatogenesis failure. iii) PMID: 39267058- hemizygous missense variant (p.Arg19Gln) in a infertile male with oliogasthenozoospermia, no functional data iv) PMID: 39189935- novel hemizygous missense variant (p.G1391R) and a recurrent variant (p.V872G) in BCORL1 from four OAT patients. Functional assays showed that the variants disturb the transcription of spermatogenetic genes such as SYCE1 and DAZL, impair the interaction with HDAC7, and cause epigenetic changes such as changes in level of histone modification with different extent, including the enhancement in acetylation of H3K14, and the reduction in acetylation of H4K5 and H4K8. Byrne et al. 2023- male fetus terminated at 22+3 GA due to abnormal renal morphology, Cleft upper lip, Median cleft palate, Ovotestis, enlarged hyroid, oral frenulae carrying hemizygous p.Tyr1692Ter called VUS- novel phenotype Sources: Literature |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Infertility and Recurrent Pregnancy Loss v0.63 | SYCE1 |
Jasmine Chew changed review comment from: Literature in OMIM: PMIM: 25062452; 25899990; 26203179- biallelic variants reported for affected individuals with POI/spermatogenic failure (NOA) New papers (biallelic variants for POI/NOA): i) PMID: 36373164- Two POI/DOR patients with biallelic LOF variants (Patient II-1 in Family 3 with compound heterozygous variants c.154C > T (p.Arg52*) and c.675del (p.Asp226Metfs*29); Patient II-1 in Family 6 with a homozygous donor splicing variant c.271 + 1G > A which led to exon 4 skipping and indel mutant p.Ala66_Leu91delinsVal). ii) PMID: 35718780- Two NOA-affected patients with different biallelic CNVs (patient 1- novel heterozygous intragenic deletion (seq[GRCh37] del(10)(10q26.3)chr10:g.135111754_135427143del) and heterozygous LOF (p.F230fs), patient 2- homozygous intragenic deletion (seq[GRCh37] del(10)(10q26.3)chr10:g.135340247_135379115del). iii) PMID: 34718620- Compound heterozygous variants (p.Glu159Lys and p.Phe230Serfs*21) in a POI patient and a homozygous variant (NM_001143764.3: c.271 + 2T > C) in a NOA patient. Sources: Literature; to: Literature in OMIM: PMIM: 25062452; 25899990; 26203179- biallelic variants reported for affected individuals with POI/spermatogenic failure (NOA) New papers (biallelic variants for POI/NOA): i) PMID: 36373164- Two POI/DOR patients with biallelic LOF variants (Patient II-1 in Family 3 with compound heterozygous variants c.154C > T (p.Arg52*) and c.675del (p.Asp226Metfs*29); Patient II-1 in Family 6 with a homozygous donor splicing variant c.271 + 1G > A which led to exon 4 skipping and indel mutant p.Ala66_Leu91delinsVal). ii) PMID: 35718780- Two NOA-affected patients with different biallelic CNVs (patient 1- novel heterozygous intragenic deletion (seq[GRCh37] del(10)(10q26.3)chr10:g.135111754_135427143del) and heterozygous LOF (p.F230fs), patient 2- homozygous intragenic deletion (seq[GRCh37] del(10)(10q26.3)chr10:g.135340247_135379115del). iii) PMID: 34718620- Compound heterozygous variants (p.Glu159Lys and p.Phe230Serfs*21) in a POI patient and a homozygous variant (NM_001143764.3: c.271 + 2T > C) in a NOA patient. Sources: Literature Mode of pathogenicity: Provide exceptions to loss-of-function |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Infertility and Recurrent Pregnancy Loss v0.63 | SYCE1 | Jasmine Chew edited their review of gene: SYCE1: Changed mode of pathogenicity: Other; Changed phenotypes: Premature ovarian failure 12, MIM# 616947, Spermatogenic failure 15 ,MIM# 616950 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Infertility and Recurrent Pregnancy Loss v0.63 | SYCE1 | Jasmine Chew edited their review of gene: SYCE1: Changed phenotypes: Premature ovarian failure 12, MIM# 616947, Spermatogenic failure 15 ,MIM#616950 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Infertility and Recurrent Pregnancy Loss v0.63 | SYCE1 |
Jasmine Chew changed review comment from: Literature in OMIM: PMIM: 25062452; 25899990; 26203179- biallelic variants reported for affected individuals with POI/spermatogenic failure (NOA) New papers (biallelic variants for POI/NOA): i) PMID: 36373164- Two POI/DOR patients with biallelic LOF variants (Patient II-1 in Family 3 with compound heterozygous variants c.154C > T (p.Arg52*) and c.675del (p.Asp226Metfs*29); Patient II-1 in Family 6 with a homozygous donor splicing variant c.271 + 1G > A which led to exon 4 skipping and indel mutant p.Ala66_Leu91delinsVal). ii) PMID: 35718780- Two NOA-affected patients with different biallelic CNVs (patient 1- novel heterozygous intragenic deletion (seq[GRCh37] del(10)(10q26.3)chr10:g.135111754_135427143del) and heterozygous LOF (p.F230fs), patient 2- homozygous intragenic deletion (seq[GRCh37] del(10)(10q26.3)chr10:g.135340247_135379115del). iii) PMID: 34718620- Compound heterozygous variants (p.Glu159Lys and p.Phe230Serfs*21) in a POI patient and a homozygous variant (NM_001143764.3: c.271 + 2T > C) in a NOA patient. Sources: Literature; to: Literature in OMIM: PMIM: 25062452; 25899990; 26203179- biallelic variants reported for affected individuals with POI/spermatogenic failure (NOA) New papers (biallelic variants for POI/NOA): i) PMID: 36373164- Two POI/DOR patients with biallelic LOF variants (Patient II-1 in Family 3 with compound heterozygous variants c.154C > T (p.Arg52*) and c.675del (p.Asp226Metfs*29); Patient II-1 in Family 6 with a homozygous donor splicing variant c.271 + 1G > A which led to exon 4 skipping and indel mutant p.Ala66_Leu91delinsVal). ii) PMID: 35718780- Two NOA-affected patients with different biallelic CNVs (patient 1- novel heterozygous intragenic deletion (seq[GRCh37] del(10)(10q26.3)chr10:g.135111754_135427143del) and heterozygous LOF (p.F230fs), patient 2- homozygous intragenic deletion (seq[GRCh37] del(10)(10q26.3)chr10:g.135340247_135379115del). iii) PMID: 34718620- Compound heterozygous variants (p.Glu159Lys and p.Phe230Serfs*21) in a POI patient and a homozygous variant (NM_001143764.3: c.271 + 2T > C) in a NOA patient. Sources: Literature |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Infertility and Recurrent Pregnancy Loss v0.63 | SYCE1 |
Jasmine Chew gene: SYCE1 was added gene: SYCE1 was added to Infertility and Pregnancy Loss. Sources: Literature Mode of inheritance for gene: SYCE1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: SYCE1 were set to 25062452; 25899990; 26203179; 36373164; 35718780; 34718620 Phenotypes for gene: SYCE1 were set to Premature ovarian failure 12, MIM# 616947, Spermatogenic failure 15 ,MIM# 616950 Mode of pathogenicity for gene: SYCE1 was set to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments Review for gene: SYCE1 was set to GREEN Added comment: Literature in OMIM: PMIM: 25062452; 25899990; 26203179- biallelic variants reported for affected individuals with POI/spermatogenic failure (NOA) New papers (biallelic variants for POI/NOA): i) PMID: 36373164- Two POI/DOR patients with biallelic LOF variants (Patient II-1 in Family 3 with compound heterozygous variants c.154C > T (p.Arg52*) and c.675del (p.Asp226Metfs*29); Patient II-1 in Family 6 with a homozygous donor splicing variant c.271 + 1G > A which led to exon 4 skipping and indel mutant p.Ala66_Leu91delinsVal). ii) PMID: 35718780- Two NOA-affected patients with different biallelic CNVs (patient 1- novel heterozygous intragenic deletion (seq[GRCh37] del(10)(10q26.3)chr10:g.135111754_135427143del) and heterozygous LOF (p.F230fs), patient 2- homozygous intragenic deletion (seq[GRCh37] del(10)(10q26.3)chr10:g.135340247_135379115del). iii) PMID: 34718620- Compound heterozygous variants (p.Glu159Lys and p.Phe230Serfs*21) in a POI patient and a homozygous variant (NM_001143764.3: c.271 + 2T > C) in a NOA patient. Sources: Literature |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||