rs104894763
Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM1BP4BP6BS2
The NM_005448.2(BMP15):c.202C>T(p.Arg68Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00111 in 1,190,144 control chromosomes in the GnomAD database, including 1 homozygotes. There are 422 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_005448.2 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -4 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.000624 AC: 70AN: 112256Hom.: 0 Cov.: 24 AF XY: 0.000639 AC XY: 22AN XY: 34428
GnomAD3 exomes AF: 0.000700 AC: 101AN: 144352Hom.: 0 AF XY: 0.000681 AC XY: 30AN XY: 44062
GnomAD4 exome AF: 0.00116 AC: 1251AN: 1077837Hom.: 1 Cov.: 33 AF XY: 0.00114 AC XY: 400AN XY: 350677
GnomAD4 genome AF: 0.000623 AC: 70AN: 112307Hom.: 0 Cov.: 24 AF XY: 0.000638 AC XY: 22AN XY: 34489
ClinVar
Submissions by phenotype
not provided Uncertain:2Benign:1
Identified in patients with premature ovarian insufficiency referred for genetic testing at GeneDx and in published literature (Di Pasquale et al., 2006); Identified in a patient with polycystic ovary syndrome and normal serum androgen levels in published literature (Crespo et al., 2022); Published functional studies demonstrate a reduction of mature protein production and decreased synergy with GDF9, however, the biological significance of these effects is uncertain (Rossetti et al., 2009; Patio et al., 2017); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 34426522, 35898701, 28359091, 19377476, 16464940, 19263482) -
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BMP15: PS4:Moderate, PS3:Supporting -
Premature ovarian failure 4 Pathogenic:1
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Ovarian dysgenesis 2 Benign:1
This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign. -
BMP15-related disorder Benign:1
This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at