3-98817870-T-C

Variant summary

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

The NM_080927.4(DCBLD2):c.1111A>G(p.Met371Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000198 in 1,613,536 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000092 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000012 (0 hom.)
• Consequence: DCBLD2 NM_080927.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.01

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=0.08624104).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DCBLD2	NM_080927.4	c.1111A>G	p.Met371Val	missense_variant	9/16	ENST00000326840.11
DCBLD2	XM_011512419.3	c.883A>G	p.Met295Val	missense_variant	8/15
DCBLD2	XM_024453348.2	c.793A>G	p.Met265Val	missense_variant	9/16

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DCBLD2	ENST00000326840.11	c.1111A>G	p.Met371Val	missense_variant	9/16	1	NM_080927.4	P1

Frequencies

GnomAD3 genomes AF: 0.0000920 AC: 14 AN: 152214 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000265

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000654

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: 0.0000147

Gnomad OTH AF: 0.000478

GnomAD3 exomes AF: 0.0000402 AC: 10 AN: 249008 Hom.: 0 AF XY: 0.0000370 AC XY: 5 AN XY: 135084

Gnomad AFR exome AF: 0.000258

Gnomad AMR exome AF: 0.000116

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: 0.0000177

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000123 AC: 18 AN: 1461204 Hom.: 0 Cov.: 32 AF XY: 0.00000963 AC XY: 7 AN XY: 726904

Gnomad4 AFR exome AF: 0.000120

Gnomad4 AMR exome AF: 0.000134

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000360

Gnomad4 OTH exome AF: 0.0000663

GnomAD4 genome AF: 0.0000919 AC: 14 AN: 152332 Hom.: 0 Cov.: 32 AF XY: 0.000107 AC XY: 8 AN XY: 74494

Gnomad4 AFR AF: 0.000265

Gnomad4 AMR AF: 0.0000653

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000147

Gnomad4 OTH AF: 0.000473

Alfa AF: 0.0000658 Hom.: 0

Bravo AF: 0.000102

ExAC AF: 0.0000331 AC: 4

EpiCase AF: 0.0000546

EpiControl AF: 0.00

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 14, 2021

The c.1111A>G (p.M371V) alteration is located in exon 9 (coding exon 9) of the DCBLD2 gene. This alteration results from a A to G substitution at nucleotide position 1111, causing the methionine (M) at amino acid position 371 to be replaced by a valine (V). 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	0.078
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.10
Cadd	Benign	15
Dann	Benign	0.90
DEOGEN2	Benign	0.26	T;.
Eigen	Benign	-0.45
Eigen_PC	Benign	-0.28
FATHMM_MKL	Benign	0.61	D
LIST_S2	Benign	0.71	T;T
M_CAP	Uncertain	0.087	D
MetaRNN	Benign	0.086	T;T
MetaSVM	Uncertain	0.28	D
MutationAssessor	Benign	0.24	N;N
MutationTaster	Benign	0.82	D;D
PrimateAI	Benign	0.38	T
PROVEAN	Benign	-1.6	N;N
REVEL	Uncertain	0.33
Sift	Benign	0.091	T;T
Sift4G	Benign	0.28	T;T
Polyphen		0.019	B;B
Vest4		0.20
MVP		0.76
MPC		0.10
ClinPred		0.018	T
GERP RS		1.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.13
gMVP		0.33

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: rs536126933; hg19: chr3-98536714;