chr6-7575273-C-CT

Position:

• chr6-7575273-C-CT

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP6_Moderate BS1

The NM_004415.4(DSP):​c.2437-11dup variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00759 in 1,120,898 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.000054 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0087 (0 hom.)
• Consequence: DSP NM_004415.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0620

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 -6 ACMG points.

• BP6: Variant 6-7575273-C-CT is Benign according to our data. Variant chr6-7575273-C-CT is described in ClinVar as [Benign]. Clinvar id is 2691165.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4_exome allele frequency = 0.00873 (8495/973522) while in subpopulation NFE AF= 0.00983 (7231/735690). AF 95% confidence interval is 0.00964. There are 0 homozygotes in gnomad4_exome. There are 3915 alleles in male gnomad4_exome subpopulation. Median coverage is 30. This position pass quality control queck.

Transcripts

RefSeq

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

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.0000543 AC: 8 AN: 147376 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000994

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000678

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000105

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000301

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00873 AC: 8495 AN: 973522 Hom.: 0 Cov.: 30 AF XY: 0.00804 AC XY: 3915 AN XY: 486828

Gnomad4 AFR exome AF: 0.00832

Gnomad4 AMR exome AF: 0.00366

Gnomad4 ASJ exome AF: 0.00546

Gnomad4 EAS exome AF: 0.00434

Gnomad4 SAS exome AF: 0.00425

Gnomad4 FIN exome AF: 0.00465

Gnomad4 NFE exome AF: 0.00983

Gnomad4 OTH exome AF: 0.00783

GnomAD4 genome AF: 0.0000543 AC: 8 AN: 147376 Hom.: 0 Cov.: 33 AF XY: 0.0000698 AC XY: 5 AN XY: 71658

Gnomad4 AFR AF: 0.0000994

Gnomad4 AMR AF: 0.0000678

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.000105

Gnomad4 NFE AF: 0.0000301

Gnomad4 OTH AF: 0.00

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Cardiomyopathy Benign:1

Benign, criteria provided, single submitter

clinical testing

CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario

Nov 09, 2022

- -

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;