6-7572029-A-G

Position:

chr6-7572029-A-G

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_004415.4(DSP):c.2091A>G(p.Gly697=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.766 in 1,613,788 control chromosomes in the GnomAD database, including 475,191 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Synonymous variant affecting the same amino acid position (i.e. G697G) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.78 ( 46213 hom., cov: 32)

Exomes 𝑓: 0.77 ( 428978 hom. )

Consequence

DSP
NM_004415.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts U:1B:13

Conservation

PhyloP100: -0.844

Variant links:

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BP6

Variant 6-7572029-A-G is Benign according to our data. Variant chr6-7572029-A-G is described in ClinVar as [Benign]. Clinvar id is 44870.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr6-7572029-A-G is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-0.844 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.793 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
DSP	NM_004415.4 linkuse as main transcript	c.2091A>G	p.Gly697=	synonymous_variant	15/24	ENST00000379802.8
DSP	NM_001319034.2 linkuse as main transcript	c.2091A>G	p.Gly697=	synonymous_variant	15/24
DSP	NM_001008844.3 linkuse as main transcript	c.2091A>G	p.Gly697=	synonymous_variant	15/24

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DSP	ENST00000379802.8 linkuse as main transcript	c.2091A>G	p.Gly697=	synonymous_variant	15/24	1	NM_004415.4	P2	P15924-1
DSP	ENST00000418664.2 linkuse as main transcript	c.2091A>G	p.Gly697=	synonymous_variant	15/24	1		A2	P15924-2
DSP	ENST00000710359.1 linkuse as main transcript	c.2091A>G	p.Gly697=	synonymous_variant	15/24			A2
DSP	ENST00000684395.1 linkuse as main transcript	n.732A>G		non_coding_transcript_exon_variant	2/5

Frequencies

GnomAD3 genomes

AF:

0.778

AC:

118340

AN:

152014

Hom.:

46193

Cov.:

show subpopulations

Gnomad AFR

AF:

0.800

Gnomad AMI

AF:

0.784

Gnomad AMR

AF:

0.789

Gnomad ASJ

AF:

0.844

Gnomad EAS

AF:

0.814

Gnomad SAS

AF:

0.688

Gnomad FIN

AF:

0.719

Gnomad MID

AF:

0.810

Gnomad NFE

AF:

0.773

Gnomad OTH

AF:

0.784

GnomAD3 exomes

AF:

0.763

AC:

191399

AN:

250974

Hom.:

73347

AF XY:

0.758

AC XY:

102864

AN XY:

135648

show subpopulations

Gnomad AFR exome

AF:

0.802

Gnomad AMR exome

AF:

0.771

Gnomad ASJ exome

AF:

0.835

Gnomad EAS exome

AF:

0.807

Gnomad SAS exome

AF:

0.683

Gnomad FIN exome

AF:

0.717

Gnomad NFE exome

AF:

0.771

Gnomad OTH exome

AF:

0.771

GnomAD4 exome

AF:

0.765

AC:

1118428

AN:

1461656

Hom.:

428978

Cov.:

AF XY:

0.764

AC XY:

555190

AN XY:

727130

show subpopulations

Gnomad4 AFR exome

AF:

0.798

Gnomad4 AMR exome

AF:

0.775

Gnomad4 ASJ exome

AF:

0.835

Gnomad4 EAS exome

AF:

0.837

Gnomad4 SAS exome

AF:

0.686

Gnomad4 FIN exome

AF:

0.715

Gnomad4 NFE exome

AF:

0.767

Gnomad4 OTH exome

AF:

0.776

GnomAD4 genome

AF:

0.778

AC:

118405

AN:

152132

Hom.:

46213

Cov.:

AF XY:

0.776

AC XY:

57701

AN XY:

74370

show subpopulations

Gnomad4 AFR

AF:

0.799

Gnomad4 AMR

AF:

0.789

Gnomad4 ASJ

AF:

0.844

Gnomad4 EAS

AF:

0.813

Gnomad4 SAS

AF:

0.689

Gnomad4 FIN

AF:

0.719

Gnomad4 NFE

AF:

0.773

Gnomad4 OTH

AF:

0.781

Alfa

AF:

0.764

Hom.:

13298

Bravo

AF:

0.789

Asia WGS

AF:

0.700

AC:

2434

AN:

3478

EpiCase

AF:

0.795

EpiControl

AF:

0.778

ClinVar

Significance: Benign

Submissions summary: Uncertain:1Benign:13

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:4

Benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	Jul 20, 2011	- -
Benign, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -
Benign, no assertion criteria provided	clinical testing	Clinical Genetics, Academic Medical Center	-	- -
Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -

not provided

Uncertain:1Benign:1

Uncertain significance, no assertion criteria provided	clinical testing	Department of Pathology and Laboratory Medicine, Sinai Health System	-	multiple AR variants in same gene - keep for nowAllele frequency is common in at least one population database (frequency: 83.525% in gnomAD_ExomesFounderPop) based on the frequency threshold of 0.5% for this gene.Variant was observed in a homozygous state in population databases more than expected for disease.A synonymous variant not located in a splice region.1 reputable source/s reports the variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation. -
Benign, criteria provided, single submitter	clinical testing	Molecular Diagnostic Laboratory for Inherited Cardiovascular Disease, Montreal Heart Institute	-	- -

Arrhythmogenic cardiomyopathy with wooly hair and keratoderma

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 30, 2021

- -

Cardiomyopathy, dilated, with wooly hair, keratoderma, and tooth agenesis

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 30, 2021

- -

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

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Feb 01, 2024

- -

Cardiomyopathy

Benign:1

Benign, criteria provided, single submitter

clinical testing

Color Diagnostics, LLC DBA Color Health

Mar 16, 2018

- -

Lethal acantholytic epidermolysis bullosa

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 30, 2021

- -

Woolly hair-skin fragility syndrome

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 30, 2021

- -

Keratosis palmoplantaris striata 2

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 30, 2021

- -

Cardiovascular phenotype

Benign:1

Benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 09, 2015

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

5.1

DANN

Benign

0.55

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over