18-67511997-A-T

Variant names:

• chr18-67511997-A-T
• rs749927031
• NM_032160.3:c.2612T>A

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_032160.3(DSEL):​c.2612T>A​(p.Leu871His) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: DSEL NM_032160.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 9.20

Genes affected

DSEL (HGNC:18144): (dermatan sulfate epimerase like) Predicted to enable chondroitin-glucuronate 5-epimerase activity. Predicted to be involved in chondroitin sulfate metabolic process and dermatan sulfate metabolic process. Predicted to be located in Golgi membrane. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000263424 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.829

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DSEL	NM_032160.3	c.2612T>A	p.Leu871His	missense_variant	Exon 2 of 2	ENST00000310045.9	NP_115536.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DSEL	ENST00000310045.9	c.2612T>A	p.Leu871His	missense_variant	Exon 2 of 2	2	NM_032160.3	ENSP00000310565.8
ENSG00000263424	ENST00000583493.1	n.1256A>T		non_coding_transcript_exon_variant	Exon 2 of 2	5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 35

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Dec 11, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.2642T>A (p.L881H) alteration is located in exon 2 (coding exon 1) of the DSEL gene. This alteration results from a T to A substitution at nucleotide position 2642, causing the leucine (L) at amino acid position 881 to be replaced by a histidine (H). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.41	D
BayesDel_noAF	Pathogenic	0.35
CADD	Pathogenic	26
DANN	Uncertain	0.98
Eigen	Pathogenic	0.73
Eigen_PC	Pathogenic	0.69
FATHMM_MKL	Pathogenic	0.99	D
M_CAP	Uncertain	0.20	D
MetaRNN	Pathogenic	0.83	D
MetaSVM	Uncertain	0.55	D
PrimateAI	Uncertain	0.71	T
PROVEAN	Uncertain	-2.6	D
REVEL	Pathogenic	0.79
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.0020	D
Vest4		0.83
MVP		0.71
MPC		0.62
ClinPred		0.98	D
GERP RS		5.1
gMVP		0.87

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

Other links and lift over

dbSNP: rs749927031; hg19: chr18-65179234;