chr1-236755096-C-T
Variant summary
Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_ModerateBP6BP7BS2
The NM_001103.4(ACTN2):c.2052C>T(p.Asn684Asn) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000539 in 1,614,108 control chromosomes in the GnomAD database, including 1 homozygotes. 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_001103.4 synonymous
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -8 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
ACTN2 | NM_001103.4 | c.2052C>T | p.Asn684Asn | synonymous_variant | Exon 17 of 21 | ENST00000366578.6 | NP_001094.1 | |
ACTN2 | NM_001278343.2 | c.2052C>T | p.Asn684Asn | synonymous_variant | Exon 17 of 21 | NP_001265272.1 | ||
ACTN2 | NR_184402.1 | n.2424C>T | non_coding_transcript_exon_variant | Exon 19 of 23 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0000394 AC: 6AN: 152220Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000107 AC: 27AN: 251476Hom.: 0 AF XY: 0.000103 AC XY: 14AN XY: 135912
GnomAD4 exome AF: 0.0000554 AC: 81AN: 1461888Hom.: 1 Cov.: 32 AF XY: 0.0000660 AC XY: 48AN XY: 727246
GnomAD4 genome AF: 0.0000394 AC: 6AN: 152220Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2AN XY: 74362
ClinVar
Submissions by phenotype
not provided Benign:2
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Dilated cardiomyopathy 1AA Uncertain: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 did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance. -
not specified Benign:1
Asn684Asn in exon 17 of ACTN2: This variant is not expected to have clinical sig nificance because it does not alter an amino acid residue and is not located wit hin the splice consensus sequence. It has been identified in 0.2% (3/1320) of Eu ropean chromosomes from a broad population by the ClinSeq Project (dbSNP rs20213 5204). -
Primary familial hypertrophic cardiomyopathy;C2677338:Dilated cardiomyopathy 1AA Benign:1
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Cardiovascular phenotype Benign:1
This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at