rs10484325

Positions:

• chr6-7556815-T-C

Variant summary

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

The NM_004415.4(DSP):​c.273+995T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.162 in 152,162 control chromosomes in the GnomAD database, including 2,217 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 0.16 (2217 hom., cov: 33)
• Consequence: DSP NM_004415.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.183

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=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.2 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DSP	NM_004415.4	c.273+995T>C		intron_variant		ENST00000379802.8	NP_004406.2
DSP	NM_001008844.3	c.273+995T>C		intron_variant			NP_001008844.1
DSP	NM_001319034.2	c.273+995T>C		intron_variant			NP_001305963.1
DSP	NM_001406591.1	c.273+995T>C		intron_variant			NP_001393520.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DSP	ENST00000379802.8	c.273+995T>C		intron_variant		1	NM_004415.4	ENSP00000369129	P2
DSP	ENST00000418664.2	c.273+995T>C		intron_variant		1		ENSP00000396591	A2
DSP	ENST00000710359.1	c.273+995T>C		intron_variant				ENSP00000518230	A2
DSP	ENST00000683563.1	n.165+995T>C		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.162 AC: 24593 AN: 152044 Hom.: 2206 Cov.: 33

Gnomad AFR AF: 0.203

Gnomad AMI AF: 0.0945

Gnomad AMR AF: 0.116

Gnomad ASJ AF: 0.198

Gnomad EAS AF: 0.00308

Gnomad SAS AF: 0.0520

Gnomad FIN AF: 0.167

Gnomad MID AF: 0.127

Gnomad NFE AF: 0.165

Gnomad OTH AF: 0.164

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

GnomAD4 genome AF: 0.162 AC: 24638 AN: 152162 Hom.: 2217 Cov.: 33 AF XY: 0.156 AC XY: 11576 AN XY: 74374

Gnomad4 AFR AF: 0.203

Gnomad4 AMR AF: 0.116

Gnomad4 ASJ AF: 0.198

Gnomad4 EAS AF: 0.00308

Gnomad4 SAS AF: 0.0526

Gnomad4 FIN AF: 0.167

Gnomad4 NFE AF: 0.165

Gnomad4 OTH AF: 0.162

Alfa AF: 0.162 Hom.: 2992

Bravo AF: 0.160

Asia WGS AF: 0.0460 AC: 159 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.5
DANN	Benign	0.52

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: rs10484325; hg19: chr6-7557048;