rs200217946
Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 2P and 7B. PP2PP3BP4_ModerateBP6BS2
The NM_017534.6(MYH2):c.3128C>T(p.Ser1043Phe) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000342 in 1,614,028 control chromosomes in the GnomAD database, including 3 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. S1043A) has been classified as Likely benign.
Frequency
Consequence
NM_017534.6 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -5 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MYH2 | NM_017534.6 | c.3128C>T | p.Ser1043Phe | missense_variant | 25/40 | ENST00000245503.10 | |
MYHAS | NR_125367.1 | n.168-38066G>A | intron_variant, non_coding_transcript_variant | ||||
MYH2 | NM_001100112.2 | c.3128C>T | p.Ser1043Phe | missense_variant | 25/40 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MYH2 | ENST00000245503.10 | c.3128C>T | p.Ser1043Phe | missense_variant | 25/40 | 1 | NM_017534.6 | P1 | |
ENST00000399342.6 | n.207-3853G>A | intron_variant, non_coding_transcript_variant | 3 |
Frequencies
GnomAD3 genomes AF: 0.000263 AC: 40AN: 152142Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000625 AC: 157AN: 251352Hom.: 1 AF XY: 0.000596 AC XY: 81AN XY: 135848
GnomAD4 exome AF: 0.000350 AC: 512AN: 1461886Hom.: 3 Cov.: 34 AF XY: 0.000348 AC XY: 253AN XY: 727242
GnomAD4 genome AF: 0.000263 AC: 40AN: 152142Hom.: 0 Cov.: 32 AF XY: 0.000161 AC XY: 12AN XY: 74326
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Women's Health and Genetics/Laboratory Corporation of America, LabCorp | Jan 12, 2024 | Variant summary: MYH2 c.3128C>T (p.Ser1043Phe) results in a non-conservative amino acid change located in the Myosin Tail domain (IPR002928) of the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 0.00062 in 251352 control chromosomes in the gnomAD database, including 1 homozygotes. To our knowledge, no occurrence of c.3128C>T in individuals affected with Myopathy, Proximal, And Ophthalmoplegia and no experimental evidence demonstrating its impact on protein function have been reported. ClinVar contains an entry for this variant (Variation ID: 321678). Based on the evidence outlined above, the variant was classified as uncertain significance. - |
Inclusion Body Myopathy, Dominant Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jun 14, 2016 | - - |
Myopathy, proximal, and ophthalmoplegia Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Dec 09, 2021 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at