3-98811473-G-T

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_Strong

The NM_080927.4(DCBLD2):c.1445C>A(p.Ala482Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00131 in 1,613,492 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0011 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0013 (2 hom.)
• Consequence: DCBLD2 NM_080927.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.29

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 Likely_benign. Variant got -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.008906305).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DCBLD2	NM_080927.4	c.1445C>A	p.Ala482Asp	missense_variant	11/16	ENST00000326840.11
DCBLD2	XM_011512419.3	c.1217C>A	p.Ala406Asp	missense_variant	10/15
DCBLD2	XM_024453348.2	c.1127C>A	p.Ala376Asp	missense_variant	11/16

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DCBLD2	ENST00000326840.11	c.1445C>A	p.Ala482Asp	missense_variant	11/16	1	NM_080927.4	P1

Frequencies

GnomAD3 genomes AF: 0.00107 AC: 163 AN: 152124 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.000217

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000917

Gnomad ASJ AF: 0.00577

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000415

Gnomad FIN AF: 0.000283

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00165

Gnomad OTH AF: 0.00144

GnomAD3 exomes AF: 0.00101 AC: 252 AN: 248878 Hom.: 0 AF XY: 0.00104 AC XY: 140 AN XY: 135016

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000349

Gnomad ASJ exome AF: 0.00447

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000163

Gnomad FIN exome AF: 0.000743

Gnomad NFE exome AF: 0.00145

Gnomad OTH exome AF: 0.00166

GnomAD4 exome AF: 0.00134 AC: 1957 AN: 1461250 Hom.: 2 Cov.: 31 AF XY: 0.00131 AC XY: 951 AN XY: 726920

Gnomad4 AFR exome AF: 0.000179

Gnomad4 AMR exome AF: 0.000291

Gnomad4 ASJ exome AF: 0.00452

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000244

Gnomad4 FIN exome AF: 0.000731

Gnomad4 NFE exome AF: 0.00151

Gnomad4 OTH exome AF: 0.00133

GnomAD4 genome AF: 0.00107 AC: 163 AN: 152242 Hom.: 0 Cov.: 33 AF XY: 0.000833 AC XY: 62 AN XY: 74438

Gnomad4 AFR AF: 0.000217

Gnomad4 AMR AF: 0.000915

Gnomad4 ASJ AF: 0.00577

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000415

Gnomad4 FIN AF: 0.000283

Gnomad4 NFE AF: 0.00165

Gnomad4 OTH AF: 0.00142

Alfa AF: 0.00123 Hom.: 0

Bravo AF: 0.000888

TwinsUK AF: 0.00108 AC: 4

ALSPAC AF: 0.000519 AC: 2

ESP6500AA AF: 0.000273 AC: 1

ESP6500EA AF: 0.00208 AC: 17

ExAC AF: 0.000927 AC: 112

EpiCase AF: 0.00191

EpiControl AF: 0.00172

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

Jul 20, 2021

The c.1445C>A (p.A482D) alteration is located in exon 11 (coding exon 11) of the DCBLD2 gene. This alteration results from a C to A substitution at nucleotide position 1445, causing the alanine (A) at amino acid position 482 to be replaced by an aspartic acid (D). 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	0.14
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Uncertain	0.040
Cadd	Benign	21
Dann	Uncertain	0.99
DEOGEN2	Benign	0.0012	T;.
Eigen	Benign	0.11
Eigen_PC	Uncertain	0.24
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Benign	0.69	T;T
M_CAP	Benign	0.054	D
MetaRNN	Benign	0.0089	T;T
MetaSVM	Uncertain	0.096	D
MutationAssessor	Benign	1.2	L;L
MutationTaster	Benign	0.73	N;N
PrimateAI	Uncertain	0.49	T
PROVEAN	Benign	-0.93	N;N
REVEL	Uncertain	0.50
Sift	Benign	0.11	T;D
Sift4G	Benign	0.26	T;T
Polyphen		0.88	P;B
Vest4		0.58
MVP		0.92
MPC		0.23
ClinPred		0.027	T
GERP RS		4.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.13
gMVP		0.67

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: rs143662022; hg19: chr3-98530317; COSMIC: COSV100472851; COSMIC: COSV100472851;