rs727502998

Variant names:

• chr6-7575273-CTTT-C
• NM_004415.4:c.2437-13_2437-11delTTT

Your query was ambiguous. Multiple possible variants found:

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

Variant summary

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

The NM_004415.4(DSP):​c.2437-13_2437-11delTTT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000934 in 1,070,684 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: 𝑓 0.0 (0 hom., cov: 33)
  • Exomes 𝑓: 9.3e-7 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: DSP NM_004415.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.536

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 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
DSP	NM_004415.4	c.2437-13_2437-11delTTT		intron_variant	Intron 17 of 23	ENST00000379802.8	NP_004406.2
DSP	NM_001319034.2	c.2437-13_2437-11delTTT		intron_variant	Intron 17 of 23		NP_001305963.1
DSP	NM_001008844.3	c.2437-13_2437-11delTTT		intron_variant	Intron 17 of 23		NP_001008844.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DSP	ENST00000379802.8	c.2437-21_2437-19delTTT		intron_variant	Intron 17 of 23	1	NM_004415.4	ENSP00000369129.3
DSP	ENST00000418664.2	c.2437-21_2437-19delTTT		intron_variant	Intron 17 of 23	1		ENSP00000396591.2
DSP	ENST00000710359.1	c.2437-21_2437-19delTTT		intron_variant	Intron 17 of 23			ENSP00000518230.1
DSP	ENST00000684395.1	n.1078-21_1078-19delTTT		intron_variant	Intron 4 of 4

Frequencies

GnomAD3 genomes AF: 0.00 AC: 0 AN: 147412 Hom.: 0 Cov.: 33 FAILED QC

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: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 9.34e-7 AC: 1 AN: 1070684 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 535018

Gnomad4 AFR exome AF: 0.0000411

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: 0.00

GnomAD4 genome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 147412 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 71686

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: 0.00

Gnomad4 OTH AF: 0.00

ClinVar

Not reported in ClinVar

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr6-7575506;