3-98800712-C-A

Variant names:

• chr3-98800712-C-A
• NM_080927.4:c.1725G>T

Variant summary

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

The NM_080927.4(DCBLD2):​c.1725G>T​(p.Trp575Cys) variant causes a missense change. 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: 32)
• Consequence: DCBLD2 NM_080927.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.95

Genes affected

DCBLD2 (HGNC:24627): (discoidin, CUB and LCCL domain containing 2) Involved in negative regulation of cell growth and wound healing. Located in cell surface. Is integral component of plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

ST3GAL6 (HGNC:18080): (ST3 beta-galactoside alpha-2,3-sialyltransferase 6) The protein encoded by this gene is a member of the sialyltransferase family. Members of this family are enzymes that transfer sialic acid from the activated cytidine 5'-monophospho-N-acetylneuraminic acid to terminal positions on sialylated glycolipids (gangliosides) or to the N- or O-linked sugar chains of glycoproteins. This protein has high specificity for neolactotetraosylceramide and neolactohexaosylceramide as glycolipid substrates and may contribute to the formation of selectin ligands and sialyl Lewis X, a carbohydrate important for cell-to-cell recognition and a blood group antigen. [provided by RefSeq, Apr 2016]

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, 0.757

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DCBLD2	NM_080927.4	c.1725G>T	p.Trp575Cys	missense_variant	Exon 15 of 16	ENST00000326840.11	NP_563615.3
DCBLD2	XM_011512419.3	c.1497G>T	p.Trp499Cys	missense_variant	Exon 14 of 15		XP_011510721.1
DCBLD2	XM_024453348.2	c.1407G>T	p.Trp469Cys	missense_variant	Exon 15 of 16		XP_024309116.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DCBLD2	ENST00000326840.11	c.1725G>T	p.Trp575Cys	missense_variant	Exon 15 of 16	1	NM_080927.4	ENSP00000321573.6
DCBLD2	ENST00000326857.9	c.1767G>T	p.Trp589Cys	missense_variant	Exon 15 of 16	1		ENSP00000321646.9
DCBLD2	ENST00000496736.1	n.377G>T		non_coding_transcript_exon_variant	Exon 2 of 3	3
ST3GAL6	ENST00000491912.1	n.254-710C>A		intron_variant	Intron 2 of 3	3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Mar 08, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1725G>T (p.W575C) alteration is located in exon 15 (coding exon 15) of the DCBLD2 gene. This alteration results from a G to T substitution at nucleotide position 1725, causing the tryptophan (W) at amino acid position 575 to be replaced by a cysteine (C). 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
AlphaMissense	Pathogenic	0.91
BayesDel_addAF	Pathogenic	0.23	D
BayesDel_noAF	Uncertain	0.10
CADD	Uncertain	25
DANN	Benign	0.97
DEOGEN2	Benign	0.0079	T;.
Eigen	Uncertain	0.59
Eigen_PC	Uncertain	0.64
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.94	D;T
M_CAP	Benign	0.018	T
MetaRNN	Uncertain	0.74	D;D
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.2	M;.
PrimateAI	Uncertain	0.77	T
PROVEAN	Benign	-1.9	N;N
REVEL	Uncertain	0.36
Sift	Benign	0.56	T;T
Sift4G	Benign	0.26	T;T
Polyphen		1.0	D;D
Vest4		0.87
MutPred		0.60		Gain of catalytic residue at W576 (P = 0.0013);.;
MVP		0.46
MPC		0.64
ClinPred		0.94	D
GERP RS		5.8
Varity_R		0.32
gMVP		0.65

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr3-98519556;