chr6-7541614-C-T

Variant names:

• chr6-7541614-C-T
• rs1182986099
• ENST00000418664.3:c.-302C>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.-302C>T 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.000012 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: DSP ENST00000418664.3 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.39
• 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=-0.23).

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.119-561G>A		intron	N/A
	DSP-AS1	NR_183329.1		n.159-561G>A		intron	N/A
	DSP-AS1	NR_183330.1		n.626-561G>A		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DSP	ENST00000418664.3	TSL:1	c.-302C>T		5_prime_UTR	Exon 1 of 24	ENSP00000396591.2	P15924-2
	DSP	ENST00000710359.2		c.-302C>T		5_prime_UTR	Exon 1 of 24	ENSP00000518230.1	P15924-3
	DSP	ENST00000713909.1		c.-302C>T		5_prime_UTR	Exon 1 of 23	ENSP00000519208.1	A0AAQ5BH17

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000115 AC: 3 AN: 259878 Hom.: 0 Cov.: 2 AF XY: 0.00000742 AC XY: 1 AN XY: 134690

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 6056

American (AMR) AF: 0.00 AC: 0 AN: 6558

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 8848

East Asian (EAS) AF: 0.00 AC: 0 AN: 18352

South Asian (SAS) AF: 0.00 AC: 0 AN: 19262

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 21008

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1232

European-Non Finnish (NFE) AF: 0.0000185 AC: 3 AN: 162140

Other (OTH) AF: 0.00 AC: 0 AN: 16422

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.0245704), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.23
CADD	Benign	20
DANN	Uncertain	0.98
PhyloP100		2.4
PromoterAI		0.015	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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: rs1182986099; hg19: chr6-7541847;