rs28763963
Variant summary
Our verdict is Benign. The variant received -11 ACMG points: 2P and 13B. PM2BP4_StrongBP6_Very_StrongBP7
The NM_004415.4(DSP):c.2247A>C(p.Leu749Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,730 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Synonymous variant affecting the same amino acid position (i.e. L749L) has been classified as Likely benign.
Frequency
Consequence
NM_004415.4 synonymous
Scores
Clinical Significance
Conservation
Publications
- arrhythmogenic right ventricular dysplasia 8Inheritance: AD, AR Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P
- keratosis palmoplantaris striata 2Inheritance: AD Classification: DEFINITIVE, STRONG, LIMITED Submitted by: G2P, Ambry Genetics, Genomics England PanelApp
- skin fragility-woolly hair-palmoplantar keratoderma syndromeInheritance: AD, AR Classification: DEFINITIVE, STRONG, SUPPORTIVE, LIMITED Submitted by: Orphanet, G2P, Genomics England PanelApp, Ambry Genetics
- arrhythmogenic cardiomyopathy with wooly hair and keratodermaInheritance: AR, AD Classification: DEFINITIVE, STRONG, MODERATE, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), G2P, Genomics England PanelApp, ClinGen, Orphanet, Ambry Genetics
- cardiomyopathy, dilated, with wooly hair, keratoderma, and tooth agenesisInheritance: AD Classification: STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), Genomics England PanelApp, Ambry Genetics
- lethal acantholytic epidermolysis bullosaInheritance: AR Classification: STRONG, MODERATE, SUPPORTIVE Submitted by: PanelApp Australia, Ambry Genetics, Labcorp Genetics (formerly Invitae), Genomics England PanelApp, Orphanet
- familial isolated dilated cardiomyopathyInheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
- striate palmoplantar keratodermaInheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
- severe dermatitis-multiple allergies-metabolic wasting syndromeInheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
- hypertrophic cardiomyopathyInheritance: AD Classification: NO_KNOWN Submitted by: ClinGen
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ACMG classification
Our verdict: Benign. The variant received -11 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
DSP | NM_004415.4 | c.2247A>C | p.Leu749Leu | synonymous_variant | Exon 16 of 24 | ENST00000379802.8 | NP_004406.2 | |
DSP | NM_001319034.2 | c.2247A>C | p.Leu749Leu | synonymous_variant | Exon 16 of 24 | NP_001305963.1 | ||
DSP | NM_001008844.3 | c.2247A>C | p.Leu749Leu | synonymous_variant | Exon 16 of 24 | NP_001008844.1 |
Ensembl
Frequencies
GnomAD3 genomes Cov.: 33
GnomAD4 exome AF: 6.84e-7 AC: 1AN: 1461730Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0AN XY: 727176 show subpopulations
GnomAD4 genome Cov.: 33
ClinVar
Submissions by phenotype
Arrhythmogenic cardiomyopathy with wooly hair and keratoderma Benign:1
- -
Arrhythmogenic right ventricular dysplasia 8;C1854063:Arrhythmogenic cardiomyopathy with wooly hair and keratoderma Benign:1
- -
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