rs786200875

Positions:

• chr18-31409555-G-GT

Variant summary

Our verdict is Pathogenic. Variant got 11 ACMG points: 11P and 0B. PVS1 PM2 PP5

The NM_177986.5(DSG4):​c.2038dupT​(p.Ser680fs) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (no stars). Variant results in nonsense mediated mRNA decay.

• Frequency: Genomes: not found (cov: 32)
• Consequence: DSG4 NM_177986.5 frameshift
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: -0.697

Genes affected

DSG4 (HGNC:21307): (desmoglein 4) This gene encodes a member of the desmoglein subgroup of desmosomal cadherins. The encoded preproprotein is proteolytically processed to generate the mature protein. This protein is a transmembrane component of desmosomes and may play a role in cell-cell adhesion in epithelial cells. Mutations in the gene are associated with localized autosomal recessive hypotrichosis and monilethrix, characterized by impaired hair growth. [provided by RefSeq, May 2016]

DSG1-AS1 (HGNC:):

ACMG classification

Verdict is Pathogenic. Variant got 11 ACMG points.

• PVS1: Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 18-31409555-G-GT is Pathogenic according to our data. Variant chr18-31409555-G-GT is described in ClinVar as [Pathogenic]. Clinvar id is 2722.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DSG4	NM_177986.5	c.2038dupT	p.Ser680fs	frameshift_variant	13/16	ENST00000308128.9	NP_817123.1
DSG4	NM_001134453.3	c.2038dupT	p.Ser680fs	frameshift_variant	13/15		NP_001127925.1
DSG1-AS1	NR_110788.1	n.156+17277dupA		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DSG4	ENST00000308128.9	c.2038dupT	p.Ser680fs	frameshift_variant	13/16	1	NM_177986.5	ENSP00000311859.4
DSG4	ENST00000359747.4	c.2038dupT	p.Ser680fs	frameshift_variant	13/15	1		ENSP00000352785.4
DSG1-AS1	ENST00000578477.5	n.156+17277dupA		intron_variant		3
DSG1-AS1	ENST00000581856.5	n.95+17277dupA		intron_variant		3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

Hypotrichosis 6 Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Jun 01, 2006

- -

Computational scores

Source: dbNSFP v4.3

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

LitVar

Other links and lift over

dbSNP: rs786200875; hg19: chr18-28989518;