chr18-31545891-A-T

Variant names:

• chr18-31545891-A-T
• NM_001943.5:c.2505A>T

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2 BP4_Moderate BP6_Moderate BP7

The NM_001943.5(DSG2):​c.2505A>T​(p.Thr835Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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. T835T) has been classified as Benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: DSG2 NM_001943.5 synonymous
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:1
• Conservation: PhyloP100: -2.77

Genes affected

DSG2 (HGNC:3049): (desmoglein 2) This gene encodes a member of the desmoglein family and cadherin cell adhesion molecule superfamily of proteins. Desmogleins are calcium-binding transmembrane glycoprotein components of desmosomes, cell-cell junctions between epithelial, myocardial, and other cell types. The encoded preproprotein is proteolytically processed to generate the mature glycoprotein. This gene is present in a gene cluster with other desmoglein gene family members on chromosome 18. Mutations in this gene have been associated with arrhythmogenic right ventricular dysplasia, familial, 10. [provided by RefSeq, Jan 2016]

DSG2-AS1 (HGNC:51311): (DSG2 antisense RNA 1)

ACMG classification

Verdict is Likely_benign. Variant got -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.44).
• BP6: Variant 18-31545891-A-T is Benign according to our data. Variant chr18-31545891-A-T is described in ClinVar as [Likely_benign]. Clinvar id is 3074984.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-2.77 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DSG2	NM_001943.5	c.2505A>T	p.Thr835Thr	synonymous_variant	Exon 15 of 15	ENST00000261590.13	NP_001934.2
DSG2	XM_047437315.1	c.1971A>T	p.Thr657Thr	synonymous_variant	Exon 16 of 16		XP_047293271.1
DSG2-AS1	NR_045216.1	n.1361T>A		non_coding_transcript_exon_variant	Exon 4 of 6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DSG2	ENST00000261590.13	c.2505A>T	p.Thr835Thr	synonymous_variant	Exon 15 of 15	1	NM_001943.5	ENSP00000261590.8
DSG2-AS1	ENST00000583706.5	n.1399T>A		non_coding_transcript_exon_variant	Exon 4 of 6	5
DSG2-AS1	ENST00000657343.1	n.712T>A		non_coding_transcript_exon_variant	Exon 4 of 4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Arrhythmogenic right ventricular cardiomyopathy Benign:1

Dec 13, 2023

All of Us Research Program, National Institutes of Health

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.44
CADD	Benign	0.13
DANN	Benign	0.68

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr18-29125854;