rs727502998

Positions:

• chr6-7575273-CTT-C
• chr6-7575273-CTT-CT
• chr6-7575273-CTT-CTTT

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP6_Moderate

The NM_004415.4(DSP):​c.2437-12_2437-11del variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000469 in 1,215,490 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.000034 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000049 (0 hom.)
• Consequence: DSP NM_004415.4 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.403

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 Likely_benign. Variant got -2 ACMG points.

• BP6: Variant 6-7575273-CTT-C is Benign according to our data. Variant chr6-7575273-CTT-C is described in ClinVar as [Likely_benign]. Clinvar id is 1625730.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DSP	NM_004415.4	c.2437-12_2437-11del		intron_variant		ENST00000379802.8	NP_004406.2
DSP	NM_001008844.3	c.2437-12_2437-11del		intron_variant			NP_001008844.1
DSP	NM_001319034.2	c.2437-12_2437-11del		intron_variant			NP_001305963.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DSP	ENST00000379802.8	c.2437-12_2437-11del		intron_variant		1	NM_004415.4	ENSP00000369129	P2
DSP	ENST00000418664.2	c.2437-12_2437-11del		intron_variant		1		ENSP00000396591	A2
DSP	ENST00000710359.1	c.2437-12_2437-11del		intron_variant				ENSP00000518230	A2
DSP	ENST00000684395.1	n.1078-12_1078-11del		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.0000339 AC: 5 AN: 147398 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000752

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.0000487 AC: 52 AN: 1068092 Hom.: 0 AF XY: 0.0000412 AC XY: 22 AN XY: 533846

Gnomad4 AFR exome AF: 0.0000412

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: 0.0000630

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.0000339 AC: 5 AN: 147398 Hom.: 0 Cov.: 33 AF XY: 0.0000279 AC XY: 2 AN XY: 71680

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000752

Gnomad4 OTH AF: 0.00

Bravo AF: 0.0000302

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Arrhythmogenic right ventricular dysplasia 8;C1854063:Arrhythmogenic cardiomyopathy with wooly hair and keratoderma Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 24, 2024

- -

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: rs727502998; hg19: chr6-7575506;