6-116436365-G-T

Variant names:

• chr6-116436365-G-T
• rs550208733
• NM_013352.4:c.1897G>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_013352.4(DSE):​c.1897G>T​(p.Val633Leu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V633M) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: DSE NM_013352.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.78
• Publications: 0 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: STRONG, MODERATE, LIMITED Submitted by: PanelApp Australia, Ambry Genetics, Labcorp Genetics (formerly Invitae), Genomics England PanelApp, G2P
• Ehlers-Danlos syndrome, musculocontractural type

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ENSG00000285446 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.11107278).

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DSE	NM_013352.4	MANE Select	c.1897G>T	p.Val633Leu	missense	Exon 6 of 6	NP_037484.1
	DSE	NM_001322939.2		c.1954G>T	p.Val652Leu	missense	Exon 6 of 6	NP_001309868.1
	DSE	NM_001080976.3		c.1897G>T	p.Val633Leu	missense	Exon 6 of 6	NP_001074445.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DSE	ENST00000644252.3	MANE Select	c.1897G>T	p.Val633Leu	missense	Exon 6 of 6	ENSP00000494147.2
	DSE	ENST00000452085.7	TSL:1	c.1897G>T	p.Val633Leu	missense	Exon 6 of 6	ENSP00000404049.2
	DSE	ENST00000359564.3	TSL:1	c.*762G>T		3_prime_UTR	Exon 5 of 5	ENSP00000352567.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.41
CADD	Benign	19
DANN	Benign	0.64
DEOGEN2	Benign	0.083	T
Eigen	Benign	-0.20
Eigen_PC	Benign	0.020
FATHMM_MKL	Uncertain	0.85	D
LIST_S2	Uncertain	0.89	D
M_CAP	Benign	0.0093	T
MetaRNN	Benign	0.11	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.69	N
PhyloP100		3.8
PrimateAI	Uncertain	0.50	T
PROVEAN	Benign	-0.49	N
REVEL	Benign	0.11
Sift	Benign	0.74	T
Sift4G	Benign	0.72	T
Polyphen		0.015	B
Vest4		0.11
MVP		0.63
MPC		0.26
ClinPred		0.13	T
GERP RS		6.0
Varity_R		0.20
gMVP		0.40
Mutation Taster		=91/9	polymorphism

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: rs550208733; hg19: chr6-116757528;