rs2285469
Variant summary
Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1
The NM_002470.4(MYH3):c.2532A>G(p.Ala844Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.675 in 1,613,870 control chromosomes in the GnomAD database, including 379,839 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Consequence
NM_002470.4 synonymous
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Benign. Variant got -21 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
MYH3 | NM_002470.4 | c.2532A>G | p.Ala844Ala | synonymous_variant | Exon 22 of 41 | ENST00000583535.6 | NP_002461.2 | |
MYH3 | XM_011523870.4 | c.2532A>G | p.Ala844Ala | synonymous_variant | Exon 22 of 41 | XP_011522172.1 | ||
MYH3 | XM_011523871.3 | c.2532A>G | p.Ala844Ala | synonymous_variant | Exon 22 of 41 | XP_011522173.1 | ||
MYH3 | XM_047436127.1 | c.2532A>G | p.Ala844Ala | synonymous_variant | Exon 24 of 43 | XP_047292083.1 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.573 AC: 87069AN: 151896Hom.: 27817 Cov.: 32
GnomAD3 exomes AF: 0.610 AC: 153466AN: 251490Hom.: 49788 AF XY: 0.622 AC XY: 84587AN XY: 135920
GnomAD4 exome AF: 0.686 AC: 1002301AN: 1461856Hom.: 352016 Cov.: 82 AF XY: 0.684 AC XY: 497675AN XY: 727234
GnomAD4 genome AF: 0.573 AC: 87102AN: 152014Hom.: 27823 Cov.: 32 AF XY: 0.568 AC XY: 42214AN XY: 74306
ClinVar
Submissions by phenotype
not specified Benign:6
- -
- -
- -
This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -
- -
- -
Freeman-Sheldon syndrome Benign:2
- -
This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -
not provided Benign:2
- -
- -
Arthrogryposis, distal, type 2B3 Benign:1
- -
Contractures, pterygia, and variable skeletal fusions syndrome 1B Benign:1
- -
Distal arthrogryposis type 2B1 Benign:1
This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -
Contractures, pterygia, and spondylocarpotarsal fusion syndrome 1A Benign:1
- -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at