chr6-7576954-T-TA
Variant summary
Our verdict is Likely benign. Variant got -1 ACMG points: 0P and 1B. BP6
The NM_004415.4(DSP):c.2794-4dup variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000415 in 1,612,572 control chromosomes in the GnomAD database, with no homozygous occurrence. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_004415.4 splice_region, splice_polypyrimidine_tract, intron
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DSP | NM_004415.4 | c.2794-4dup | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant | ENST00000379802.8 | |||
DSP | NM_001008844.3 | c.2794-4dup | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant | ||||
DSP | NM_001319034.2 | c.2794-4dup | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DSP | ENST00000379802.8 | c.2794-4dup | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant | 1 | NM_004415.4 | P2 | |||
DSP | ENST00000418664.2 | c.2794-4dup | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant | 1 | A2 | ||||
DSP | ENST00000710359.1 | c.2794-4dup | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant | A2 |
Frequencies
GnomAD3 genomes AF: 0.000197 AC: 30AN: 152250Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000519 AC: 13AN: 250666Hom.: 0 AF XY: 0.0000369 AC XY: 5AN XY: 135472
GnomAD4 exome AF: 0.0000247 AC: 36AN: 1460204Hom.: 0 Cov.: 30 AF XY: 0.0000193 AC XY: 14AN XY: 726282
GnomAD4 genome AF: 0.000203 AC: 31AN: 152368Hom.: 0 Cov.: 33 AF XY: 0.000242 AC XY: 18AN XY: 74516
ClinVar
Submissions by phenotype
not specified Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | Women's Health and Genetics/Laboratory Corporation of America, LabCorp | May 22, 2023 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Jan 28, 2015 | Variant classified as Uncertain Significance - Favor Benign. The c.2794-4_2794-3 insA variant in DSP has been previously reported by our laboratory in 2 African American individuals, 1 with DCM and 1 with an unspecified cardiomyopathy. It h as also been identified in 0.1% (12/10132) of African chromosomes by the Exome A ggregation Consortium (ExAC, http://exac.broadinstitute.org; dbSNP rs397516924). This variant is located in the 3' splice region. Computational tools do not sug gest an impact to splicing. However, this information is not predictive enough t o rule out pathogenicity. In summary, while the clinical significance of the c.2 794-4_2794-3insA variant is uncertain, its frequency suggests that it is more li kely to be benign. - |
Arrhythmogenic right ventricular dysplasia 8;C1854063:Arrhythmogenic cardiomyopathy with wooly hair and keratoderma Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 11, 2024 | - - |
Cardiomyopathy Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Color Diagnostics, LLC DBA Color Health | Apr 15, 2019 | - - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Dec 28, 2022 | See Variant Classification Assertion Criteria. - |
Cardiovascular phenotype Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Jun 29, 2023 | 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