rs1555637241

Variant names:

• chr18-31069033-C-G
• NM_024422.6:c.2369G>C

Your query was ambiguous. Multiple possible variants found:

• chr18-31069033-C-G
• chr18-31069033-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_024422.6(DSC2):​c.2369G>C​(p.Gly790Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,460,614 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: DSC2 NM_024422.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.93

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DSC2	NM_024422.6	c.2369G>C	p.Gly790Ala	missense_variant	Exon 15 of 16	ENST00000280904.11	NP_077740.1
DSC2	NM_004949.5	c.2369G>C	p.Gly790Ala	missense_variant	Exon 15 of 17		NP_004940.1
DSC2	NM_001406506.1	c.1940G>C	p.Gly647Ala	missense_variant	Exon 15 of 16		NP_001393435.1
DSC2	NM_001406507.1	c.1940G>C	p.Gly647Ala	missense_variant	Exon 15 of 17		NP_001393436.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DSC2	ENST00000280904.11	c.2369G>C	p.Gly790Ala	missense_variant	Exon 15 of 16	1	NM_024422.6	ENSP00000280904.6
DSC2	ENST00000251081.8	c.2369G>C	p.Gly790Ala	missense_variant	Exon 15 of 17	1		ENSP00000251081.6
DSC2	ENST00000648081.1	c.1940G>C	p.Gly647Ala	missense_variant	Exon 16 of 17			ENSP00000497441.1
DSC2	ENST00000682357.1	c.1940G>C	p.Gly647Ala	missense_variant	Exon 15 of 16			ENSP00000507826.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1460614 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 726618

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.0000166

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	0.0077	T
BayesDel_noAF	Benign	-0.23
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.12	T;.;.
Eigen	Uncertain	0.37
Eigen_PC	Uncertain	0.24
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Uncertain	0.88	D;D;D
M_CAP	Pathogenic	0.34	D
MetaRNN	Uncertain	0.54	D;D;D
MetaSVM	Uncertain	0.33	D
MutationAssessor	Pathogenic	3.1	M;M;.
PrimateAI	Benign	0.32	T
PROVEAN	Uncertain	-3.7	D;D;.
REVEL	Benign	0.23
Sift	Uncertain	0.023	D;D;.
Sift4G	Uncertain	0.021	D;D;.
Polyphen		1.0	D;D;.
Vest4		0.28
MutPred		0.26		Loss of sheet (P = 0.0054);Loss of sheet (P = 0.0054);.;
MVP		0.87
MPC		0.23
ClinPred		0.95	D
GERP RS		3.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.26
gMVP		0.42

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: chr18-28648999;