Genetic Variant NM_013352.4:c.1926T>C (chr6-116436394-T-C) – ACMG Classification: Benign (-21 pts)

Variant summary

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

The NM_013352.4(DSE):c.1926T>C(p.Asn642Asn) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.938 in 1,614,096 control chromosomes in the GnomAD database, including 710,142 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.96 ( 69521 hom., cov: 30)

Exomes 𝑓: 0.94 ( 640621 hom. )

Consequence

DSE
NM_013352.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.0270

Variant links:

Genes affected

DSE (HGNC:21144): (dermatan sulfate epimerase) The protein encoded by this gene is a tumor-rejection antigen. It is localized to the endoplasmic reticulum and functions to convert D-glucuronic acid to L-iduronic acid during the biosynthesis of dermatan sulfate. This antigen possesses tumor epitopes capable of inducing HLA-A24-restricted and tumor-specific cytotoxic T lymphocytes in cancer patients and may be useful for specific immunotherapy. Mutations in this gene cause inmusculocontractural Ehlers-Danlos syndrome. Alternative splicing results in multiple transcript variants. A related pseudogene has been identified on chromosome 9, and a paralogous gene exists on chromosome 18. [provided by RefSeq, Apr 2016]

DSE links:

ENSG00000285446 (HGNC:):

ENSG00000285446 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.64).

BP6

Variant 6-116436394-T-C is Benign according to our data. Variant chr6-116436394-T-C is described in ClinVar as [Benign]. Clinvar id is 1166942.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr6-116436394-T-C is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-0.027 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.98 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DSE	NM_013352.4 link	c.1926T>C	p.Asn642Asn	synonymous_variant	Exon 6 of 6	ENST00000644252.3	NP_037484.1	Q9UL01

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DSE	ENST00000644252.3 link	c.1926T>C	p.Asn642Asn	synonymous_variant	Exon 6 of 6		NM_013352.4	ENSP00000494147.2		Q9UL01
ENSG00000285446	ENST00000644499.1 link	c.766+5201T>C		intron_variant	Intron 3 of 3			ENSP00000495266.1		A0A2R8Y6J1

Frequencies

GnomAD3 genomes

AF:

0.955

AC:

145283

AN:

152108

Hom.:

69461

Cov.:

show subpopulations

Gnomad AFR

AF:

0.988

Gnomad AMI

AF:

0.944

Gnomad AMR

AF:

0.959

Gnomad ASJ

AF:

0.969

Gnomad EAS

AF:

0.995

Gnomad SAS

AF:

0.983

Gnomad FIN

AF:

0.962

Gnomad MID

AF:

0.981

Gnomad NFE

AF:

0.928

Gnomad OTH

AF:

0.953

GnomAD3 exomes

AF:

0.954

AC:

239609

AN:

251204

Hom.:

114364

AF XY:

0.953

AC XY:

129442

AN XY:

135756

show subpopulations

Gnomad AFR exome

AF:

0.989

Gnomad AMR exome

AF:

0.967

Gnomad ASJ exome

AF:

0.967

Gnomad EAS exome

AF:

0.999

Gnomad SAS exome

AF:

0.978

Gnomad FIN exome

AF:

0.959

Gnomad NFE exome

AF:

0.929

Gnomad OTH exome

AF:

0.947

GnomAD4 exome

AF:

0.936

AC:

1368178

AN:

1461870

Hom.:

640621

Cov.:

AF XY:

0.937

AC XY:

681353

AN XY:

727240

show subpopulations

Gnomad4 AFR exome

AF:

0.990

Gnomad4 AMR exome

AF:

0.966

Gnomad4 ASJ exome

AF:

0.969

Gnomad4 EAS exome

AF:

0.989

Gnomad4 SAS exome

AF:

0.977

Gnomad4 FIN exome

AF:

0.955

Gnomad4 NFE exome

AF:

0.926

Gnomad4 OTH exome

AF:

0.946

GnomAD4 genome

AF:

0.955

AC:

145402

AN:

152226

Hom.:

69521

Cov.:

AF XY:

0.958

AC XY:

71277

AN XY:

74414

show subpopulations

Gnomad4 AFR

AF:

0.988

Gnomad4 AMR

AF:

0.959

Gnomad4 ASJ

AF:

0.969

Gnomad4 EAS

AF:

0.995

Gnomad4 SAS

AF:

0.983

Gnomad4 FIN

AF:

0.962

Gnomad4 NFE

AF:

0.928

Gnomad4 OTH

AF:

0.953

Alfa

AF:

0.937

Hom.:

66324

Bravo

AF:

0.956

Asia WGS

AF:

0.989

AC:

3440

AN:

3478

EpiCase

AF:

0.935

EpiControl

AF:

0.932

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Ehlers-Danlos syndrome, musculocontractural type 2

Benign:2

Jul 30, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.64

CADD

Benign

1.0

DANN

Benign

0.56

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