rs375164626
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM5BP4BS2_Supporting
The NM_001164508.2(NEB):c.7309C>T(p.Arg2437Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000143 in 1,613,680 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R2437Q) has been classified as Likely benign.
Frequency
Consequence
NM_001164508.2 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
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NEB | ENST00000397345.8 | c.7309C>T | p.Arg2437Trp | missense_variant | Exon 54 of 182 | 5 | NM_001164508.2 | ENSP00000380505.3 | ||
NEB | ENST00000427231.7 | c.7309C>T | p.Arg2437Trp | missense_variant | Exon 54 of 182 | 5 | NM_001164507.2 | ENSP00000416578.2 | ||
NEB | ENST00000409198.5 | c.7309C>T | p.Arg2437Trp | missense_variant | Exon 54 of 150 | 5 | ENSP00000386259.1 |
Frequencies
GnomAD3 genomes AF: 0.000132 AC: 20AN: 152074Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000165 AC: 41AN: 248974Hom.: 0 AF XY: 0.000178 AC XY: 24AN XY: 135056
GnomAD4 exome AF: 0.000144 AC: 210AN: 1461606Hom.: 2 Cov.: 31 AF XY: 0.000164 AC XY: 119AN XY: 727092
GnomAD4 genome AF: 0.000132 AC: 20AN: 152074Hom.: 0 Cov.: 32 AF XY: 0.000121 AC XY: 9AN XY: 74286
ClinVar
Submissions by phenotype
not provided Uncertain:4
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NEB: PM2, BP1, BP4 -
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: 27105866, 25214167, 34426522) -
Nemaline myopathy 2 Uncertain:2Benign:1
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This variant was determined to be of uncertain significance according to ACMG Guidelines, 2015 [PMID:25741868]. -
Nemaline myopathy 2;C5543431:Arthrogryposis multiplex congenita 6 Uncertain:1
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at