rs886061738

Variant names:

• chr6-7541656-A-G
• rs886061738
• ENST00000418664.3:c.-260A>G

Your query was ambiguous. Multiple possible variants found:

• chr6-7541656-A-G
• chr6-7541656-A-T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The ENST00000418664.3(DSP):​c.-260A>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: DSP ENST00000418664.3 5_prime_UTR
• Clinical Significance: Uncertain significance criteria provided, single submitter U:4
• Conservation: PhyloP100: -0.0500
• Publications: 0 publications found

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]

DSP-AS1 (HGNC:56039): (DSP antisense RNA 1)

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.46).

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000418664.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DSP-AS1	NR_183328.1		n.119-603T>C		intron	N/A
	DSP-AS1	NR_183329.1		n.159-603T>C		intron	N/A
	DSP-AS1	NR_183330.1		n.626-603T>C		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DSP	ENST00000418664.3	TSL:1	c.-260A>G		5_prime_UTR	Exon 1 of 24	ENSP00000396591.2	P15924-2
	DSP	ENST00000710359.2		c.-260A>G		5_prime_UTR	Exon 1 of 24	ENSP00000518230.1	P15924-3
	DSP	ENST00000713909.1		c.-260A>G		5_prime_UTR	Exon 1 of 23	ENSP00000519208.1	A0AAQ5BH17

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 373482 Hom.: 0 Cov.: 3 AF XY: 0.00 AC XY: 0 AN XY: 195492

African (AFR) AF: 0.00 AC: 0 AN: 7548

American (AMR) AF: 0.00 AC: 0 AN: 11746

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 11560

East Asian (EAS) AF: 0.00 AC: 0 AN: 24130

South Asian (SAS) AF: 0.00 AC: 0 AN: 34552

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 27960

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1730

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 231784

Other (OTH) AF: 0.00 AC: 0 AN: 22472

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	Arrhythmogenic right ventricular cardiomyopathy (1)
-	1	-	Epidermolysis bullosa simplex due to plakophilin deficiency (1)
-	1	-	Lethal acantholytic epidermolysis bullosa (1)
-	1	-	Woolly hair-skin fragility syndrome (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.46
CADD	Benign	13
DANN	Benign	0.87
PhyloP100		-0.050
PromoterAI		-0.055	Neutral

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

Other links and lift over

dbSNP: rs886061738; hg19: chr6-7541889;