rs2744371

Positions:

• chr6-7553941-A-C
• chr6-7553941-A-G
• chr6-7553941-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004415.4(DSP):​c.171-1777A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.254 in 152,254 control chromosomes in the GnomAD database, including 5,262 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.25 (5262 hom., cov: 33)
• Consequence: DSP NM_004415.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.35

Genes affected

DSP (HGNC:3052): (desmoplakin) This gene encodes a protein that anchors intermediate filaments to desmosomal plaques and forms an obligate component of functional desmosomes. Mutations in this gene are the cause of several cardiomyopathies and keratodermas, including skin fragility-woolly hair syndrome. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2016]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.76).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.335 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DSP	NM_004415.4	c.171-1777A>C		intron_variant		ENST00000379802.8	NP_004406.2
DSP	NM_001008844.3	c.171-1777A>C		intron_variant			NP_001008844.1
DSP	NM_001319034.2	c.171-1777A>C		intron_variant			NP_001305963.1
DSP	NM_001406591.1	c.171-1777A>C		intron_variant			NP_001393520.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DSP	ENST00000379802.8	c.171-1777A>C		intron_variant		1	NM_004415.4	ENSP00000369129	P2

Frequencies

GnomAD3 genomes AF: 0.254 AC: 38628 AN: 152138 Hom.: 5248 Cov.: 33

Gnomad AFR AF: 0.339

Gnomad AMI AF: 0.186

Gnomad AMR AF: 0.204

Gnomad ASJ AF: 0.305

Gnomad EAS AF: 0.0565

Gnomad SAS AF: 0.219

Gnomad FIN AF: 0.210

Gnomad MID AF: 0.275

Gnomad NFE AF: 0.236

Gnomad OTH AF: 0.256

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.254 AC: 38675 AN: 152254 Hom.: 5262 Cov.: 33 AF XY: 0.251 AC XY: 18680 AN XY: 74430

Gnomad4 AFR AF: 0.339

Gnomad4 AMR AF: 0.204

Gnomad4 ASJ AF: 0.305

Gnomad4 EAS AF: 0.0557

Gnomad4 SAS AF: 0.218

Gnomad4 FIN AF: 0.210

Gnomad4 NFE AF: 0.236

Gnomad4 OTH AF: 0.255

Alfa AF: 0.143 Hom.: 340

Bravo AF: 0.257

Asia WGS AF: 0.177 AC: 617 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	10
DANN	Benign	0.83

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: rs2744371; hg19: chr6-7554174;