3-98808138-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_080927.4(DCBLD2):c.1613T>C(p.Val538Ala) variant causes a missense change. The variant allele was found at a frequency of 0.0000983 in 1,607,042 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00047 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000060 (0 hom.)
• Consequence: DCBLD2 NM_080927.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.66

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.14800787).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DCBLD2	NM_080927.4	c.1613T>C	p.Val538Ala	missense_variant	13/16	ENST00000326840.11
DCBLD2	XM_011512419.3	c.1385T>C	p.Val462Ala	missense_variant	12/15
DCBLD2	XM_024453348.2	c.1295T>C	p.Val432Ala	missense_variant	13/16

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DCBLD2	ENST00000326840.11	c.1613T>C	p.Val538Ala	missense_variant	13/16	1	NM_080927.4	P1

Frequencies

GnomAD3 genomes AF: 0.000466 AC: 71 AN: 152200 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00166

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000655

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.000478

GnomAD3 exomes AF: 0.0000744 AC: 18 AN: 241870 Hom.: 0 AF XY: 0.0000609 AC XY: 8 AN XY: 131304

Gnomad AFR exome AF: 0.00107

Gnomad AMR exome AF: 0.0000309

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.000171

GnomAD4 exome AF: 0.0000598 AC: 87 AN: 1454724 Hom.: 0 Cov.: 30 AF XY: 0.0000608 AC XY: 44 AN XY: 723424

Gnomad4 AFR exome AF: 0.00154

Gnomad4 AMR exome AF: 0.000161

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000118

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000171

Gnomad4 OTH exome AF: 0.000117

GnomAD4 genome AF: 0.000466 AC: 71 AN: 152318 Hom.: 0 Cov.: 32 AF XY: 0.000470 AC XY: 35 AN XY: 74492

Gnomad4 AFR AF: 0.00166

Gnomad4 AMR AF: 0.0000654

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.000473

Alfa AF: 0.000109 Hom.: 0

Bravo AF: 0.000510

ESP6500AA AF: 0.000733 AC: 3

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.0000827 AC: 10

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 21, 2023

The c.1613T>C (p.V538A) alteration is located in exon 13 (coding exon 13) of the DCBLD2 gene. This alteration results from a T to C substitution at nucleotide position 1613, causing the valine (V) at amino acid position 538 to be replaced by an alanine (A). 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	Benign	0.32
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Uncertain	-0.010
Cadd	Uncertain	25
Dann	Uncertain	1.0
DEOGEN2	Benign	0.011	T;.
Eigen	Uncertain	0.26
Eigen_PC	Uncertain	0.33
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Benign	0.70	T;T
M_CAP	Uncertain	0.24	D
MetaRNN	Benign	0.15	T;T
MetaSVM	Uncertain	0.55	D
MutationAssessor	Uncertain	2.2	M;M
MutationTaster	Benign	1.0	D;D
PrimateAI	Uncertain	0.63	T
PROVEAN	Benign	-1.8	N;N
REVEL	Uncertain	0.50
Sift	Benign	0.13	T;D
Sift4G	Uncertain	0.052	T;T
Polyphen		0.022	B;D
Vest4		0.63
MVP		0.93
MPC		0.54
ClinPred		0.092	T
GERP RS		4.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.090
gMVP		0.66

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: rs201629117; hg19: chr3-98526982;