chr18-31101909-G-C

Variant names:

• chr18-31101909-G-C
• rs1463773872
• NM_024422.6:c.63C>G

Variant summary

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

The NM_024422.6(DSC2):​c.63C>G​(p.Thr21Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000725 in 1,379,514 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. T21T) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.2e-7 (0 hom.)
• Consequence: DSC2 NM_024422.6 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.603
• Publications: 0 publications found

Genes affected

DSC2 (HGNC:3036): (desmocollin 2) This gene encodes a member of the desmocollin protein subfamily. Desmocollins, along with desmogleins, are cadherin-like transmembrane glycoproteins that are major components of the desmosome. Desmosomes are cell-cell junctions that help resist shearing forces and are found in high concentrations in cells subject to mechanical stress. This gene is found in a cluster with other desmocollin family members on chromosome 18. Mutations in this gene are associated with arrhythmogenic right ventricular dysplasia-11, and reduced protein expression has been described in several types of cancer. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Feb 2015]

DSCAS (HGNC:51116): (DSC1/DSC2 antisense RNA)

ACMG classification

Our verdict: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.43).
• BP6: Variant 18-31101909-G-C is Benign according to our data. Variant chr18-31101909-G-C is described in ClinVar as Likely_benign. ClinVar VariationId is 3614072.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.603 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024422.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DSC2	NM_024422.6	MANE Select	c.63C>G	p.Thr21Thr	synonymous	Exon 1 of 16	NP_077740.1	Q02487-1
	DSC2	NM_004949.5		c.63C>G	p.Thr21Thr	synonymous	Exon 1 of 17	NP_004940.1	Q02487-2
	DSCAS	NR_110785.1		n.136+186G>C		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DSC2	ENST00000280904.11	TSL:1 MANE Select	c.63C>G	p.Thr21Thr	synonymous	Exon 1 of 16	ENSP00000280904.6	Q02487-1
	DSC2	ENST00000251081.8	TSL:1	c.63C>G	p.Thr21Thr	synonymous	Exon 1 of 17	ENSP00000251081.6	Q02487-2
	DSC2	ENST00000713707.1		c.63C>G	p.Thr21Thr	synonymous	Exon 1 of 16	ENSP00000519010.1	A0AAQ5BGP6

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.25e-7 AC: 1 AN: 1379514 Hom.: 0 Cov.: 32 AF XY: 0.00000147 AC XY: 1 AN XY: 680796

African (AFR) AF: 0.00 AC: 0 AN: 30562

American (AMR) AF: 0.00 AC: 0 AN: 35130

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24960

East Asian (EAS) AF: 0.00 AC: 0 AN: 35014

South Asian (SAS) AF: 0.00 AC: 0 AN: 78270

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 36038

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5640

European-Non Finnish (NFE) AF: 9.29e-7 AC: 1 AN: 1076228

Other (OTH) AF: 0.00 AC: 0 AN: 57672

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	Arrhythmogenic right ventricular dysplasia 11 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.43
CADD	Benign	9.3
DANN	Benign	0.85
PhyloP100		0.60
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

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

Other links and lift over

dbSNP: rs1463773872; hg19: chr18-28681872;