Genetic Variant DSE:p.Asn642Lys (chr6-116436394-T-A) – ACMG Classification: Uncertain_significance (4 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM1PM2

The NM_013352.4(DSE):c.1926T>A(p.Asn642Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. N642N) has been classified as Benign.

Frequency

Genomes: not found (cov: 30)

Consequence

DSE
NM_013352.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0270

Publications

17 publications found

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 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

DSE links:

ENSG00000285446 (HGNC:):

ENSG00000285446 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

PM1

In a glycosylation_site N-linked (GlcNAc...) (complex) asparagine (size 0) in uniprot entity DSE_HUMAN

PM2

Very rare variant in population databases, with high coverage;

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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
DSE	NM_013352.4	MANE Select	c.1926T>A	p.Asn642Lys	missense	Exon 6 of 6	NP_037484.1	Q9UL01
DSE	NM_001322939.2		c.1983T>A	p.Asn661Lys	missense	Exon 6 of 6	NP_001309868.1	B7Z765
DSE	NM_001080976.3		c.1926T>A	p.Asn642Lys	missense	Exon 6 of 6	NP_001074445.1	Q9UL01

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
DSE	ENST00000644252.3	MANE Select	c.1926T>A	p.Asn642Lys	missense	Exon 6 of 6	ENSP00000494147.2	Q9UL01
DSE	ENST00000452085.7	TSL:1	c.1926T>A	p.Asn642Lys	missense	Exon 6 of 6	ENSP00000404049.2	Q9UL01
DSE	ENST00000359564.3	TSL:1	c.*791T>A		3_prime_UTR	Exon 5 of 5	ENSP00000352567.3	A0A2U3TZJ0

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.56

BayesDel_addAF

Benign

-0.11

BayesDel_noAF

Benign

-0.40

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.097

Eigen

Benign

-0.34

Eigen_PC

Benign

-0.45

FATHMM_MKL

Uncertain

0.80

LIST_S2

Uncertain

0.92

M_CAP

Benign

0.029

MetaRNN

Uncertain

0.52

MetaSVM

Benign

-0.56

MutationAssessor

Uncertain

2.1

PhyloP100

-0.027

PrimateAI

Uncertain

0.72

PROVEAN

Benign

0.49

REVEL

Benign

0.27

Sift

Benign

0.27

Sift4G

Benign

0.42

Polyphen

1.0

Vest4

0.54

MVP

0.53

MPC

0.89

ClinPred

0.45

GERP RS

-5.2

Varity_R

0.47

gMVP

0.73

Mutation Taster

=13/87

disease causing

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over