3-98819268-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_080927.4(DCBLD2):c.1021G>A(p.Ala341Thr) variant causes a missense change. The variant allele was found at a frequency of 0.000338 in 1,611,736 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 0.00031 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00034 (0 hom.)
• Consequence: DCBLD2 NM_080927.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.49

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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.31770468).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DCBLD2	NM_080927.4	c.1021G>A	p.Ala341Thr	missense_variant	8/16	ENST00000326840.11
DCBLD2	XM_011512419.3	c.793G>A	p.Ala265Thr	missense_variant	7/15
DCBLD2	XM_024453348.2	c.703G>A	p.Ala235Thr	missense_variant	8/16

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DCBLD2	ENST00000326840.11	c.1021G>A	p.Ala341Thr	missense_variant	8/16	1	NM_080927.4	P1

Frequencies

GnomAD3 genomes AF: 0.000309 AC: 47 AN: 152120 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000724

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000655

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000603

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.000315 AC: 77 AN: 244646 Hom.: 0 AF XY: 0.000369 AC XY: 49 AN XY: 132818

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000236

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000995

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000597

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000341 AC: 498 AN: 1459500 Hom.: 0 Cov.: 31 AF XY: 0.000350 AC XY: 254 AN XY: 725808

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.000271

Gnomad4 ASJ exome AF: 0.0000383

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000163

Gnomad4 FIN exome AF: 0.0000563

Gnomad4 NFE exome AF: 0.000395

Gnomad4 OTH exome AF: 0.000431

GnomAD4 genome AF: 0.000309 AC: 47 AN: 152236 Hom.: 0 Cov.: 32 AF XY: 0.000188 AC XY: 14 AN XY: 74456

Gnomad4 AFR AF: 0.0000722

Gnomad4 AMR AF: 0.0000654

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000603

Gnomad4 OTH AF: 0.00

Alfa AF: 0.000501 Hom.: 1

Bravo AF: 0.000363

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000734 AC: 6

ExAC AF: 0.000290 AC: 35

Asia WGS AF: 0.000289 AC: 1 AN: 3478

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

Jun 21, 2021

The c.1021G>A (p.A341T) alteration is located in exon 8 (coding exon 8) of the DCBLD2 gene. This alteration results from a G to A substitution at nucleotide position 1021, causing the alanine (A) at amino acid position 341 to be replaced by a threonine (T). 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	0.31
BayesDel_addAF	Benign	-0.059	T
BayesDel_noAF	Uncertain	0.040
Cadd	Pathogenic	27
Dann	Uncertain	1.0
DEOGEN2	Benign	0.27	T;.
Eigen	Benign	0.15
Eigen_PC	Uncertain	0.26
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.87	D;D
M_CAP	Uncertain	0.099	D
MetaRNN	Benign	0.32	T;T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	1.0	L;L
MutationTaster	Benign	1.0	D;D
PrimateAI	Benign	0.45	T
PROVEAN	Uncertain	-2.6	D;D
REVEL	Uncertain	0.60
Sift	Uncertain	0.0030	D;T
Sift4G	Benign	0.13	T;T
Polyphen		0.96	D;B
Vest4		0.60
MVP		0.95
MPC		0.21
ClinPred		0.24	T
GERP RS		5.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.36
gMVP		0.36

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: rs200822370; hg19: chr3-98538112;