rs560644

Variant names:

• chr6-116436394-T-C
• rs560644
• NM_013352.4:c.1926T>C

Your query was ambiguous. Multiple possible variants found:

• chr6-116436394-T-C
• chr6-116436394-T-A

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.0270
• Publications: 17 publications found

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 Gene-Disease associations (from GenCC):

• Ehlers-Danlos syndrome, musculocontractural type 2

  Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE, LIMITED Submitted by: Ambry Genetics, ClinGen, G2P, Genomics England PanelApp, Labcorp Genetics (formerly Invitae)
• Ehlers-Danlos syndrome, musculocontractural type

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ENSG00000285446 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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 VariationId is 1166942.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_013352.4. 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
	DSE	NM_013352.4	MANE Select	c.1926T>C	p.Asn642Asn	synonymous	Exon 6 of 6	NP_037484.1	Q9UL01
	DSE	NM_001322939.2		c.1983T>C	p.Asn661Asn	synonymous	Exon 6 of 6	NP_001309868.1	B7Z765
	DSE	NM_001080976.3		c.1926T>C	p.Asn642Asn	synonymous	Exon 6 of 6	NP_001074445.1	Q9UL01

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DSE	ENST00000644252.3	MANE Select	c.1926T>C	p.Asn642Asn	synonymous	Exon 6 of 6	ENSP00000494147.2	Q9UL01
	DSE	ENST00000452085.7	TSL:1	c.1926T>C	p.Asn642Asn	synonymous	Exon 6 of 6	ENSP00000404049.2	Q9UL01
	DSE	ENST00000359564.3	TSL:1	c.*791T>C		3_prime_UTR	Exon 5 of 5	ENSP00000352567.3	A0A2U3TZJ0

Frequencies

GnomAD3 genomes AF: 0.955 AC: 145283 AN: 152108 Hom.: 69461 Cov.: 30

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

GnomAD2 exomes AF: 0.954 AC: 239609 AN: 251204 AF XY: 0.953

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 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.: 94 AF XY: 0.937 AC XY: 681353 AN XY: 727240

African (AFR) AF: 0.990 AC: 33126 AN: 33476

American (AMR) AF: 0.966 AC: 43195 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.969 AC: 25333 AN: 26136

East Asian (EAS) AF: 0.989 AC: 39255 AN: 39700

South Asian (SAS) AF: 0.977 AC: 84301 AN: 86258

European-Finnish (FIN) AF: 0.955 AC: 51022 AN: 53418

Middle Eastern (MID) AF: 0.977 AC: 5638 AN: 5768

European-Non Finnish (NFE) AF: 0.926 AC: 1029190 AN: 1111996

Other (OTH) AF: 0.946 AC: 57118 AN: 60396

GnomAD4 genome AF: 0.955 AC: 145402 AN: 152226 Hom.: 69521 Cov.: 30 AF XY: 0.958 AC XY: 71277 AN XY: 74414

African (AFR) AF: 0.988 AC: 41044 AN: 41538

American (AMR) AF: 0.959 AC: 14663 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.969 AC: 3363 AN: 3470

East Asian (EAS) AF: 0.995 AC: 5155 AN: 5180

South Asian (SAS) AF: 0.983 AC: 4733 AN: 4816

European-Finnish (FIN) AF: 0.962 AC: 10197 AN: 10602

Middle Eastern (MID) AF: 0.983 AC: 289 AN: 294

European-Non Finnish (NFE) AF: 0.928 AC: 63084 AN: 68010

Other (OTH) AF: 0.953 AC: 2013 AN: 2112

Alfa AF: 0.942 Hom.: 84065

Bravo AF: 0.956

Asia WGS AF: 0.989 AC: 3440 AN: 3478

EpiCase AF: 0.935

EpiControl AF: 0.932

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	Ehlers-Danlos syndrome, musculocontractural type 2 (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.64
CADD	Benign	1.0
DANN	Benign	0.56
PhyloP100		-0.027
Mutation Taster		=98/2	polymorphism (auto)

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: rs560644; hg19: chr6-116757557; COSMIC: COSV108165152; COSMIC: COSV108165152;