3-98819255-G-A

Variant summary

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

The NM_080927.4(DCBLD2):c.1034C>T(p.Thr345Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000615 in 1,608,892 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 0.000020 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000066 ( 2 hom. )

Consequence

DCBLD2
NM_080927.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.05

Variant links:

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]

DCBLD2 links:

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]

ST3GAL6 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.057980567).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
DCBLD2	NM_080927.4 linkuse as main transcript	c.1034C>T	p.Thr345Ile	missense_variant	8/16	ENST00000326840.11
DCBLD2	XM_011512419.3 linkuse as main transcript	c.806C>T	p.Thr269Ile	missense_variant	7/15
DCBLD2	XM_024453348.2 linkuse as main transcript	c.716C>T	p.Thr239Ile	missense_variant	8/16

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DCBLD2	ENST00000326840.11 linkuse as main transcript	c.1034C>T	p.Thr345Ile	missense_variant	8/16	1	NM_080927.4	P1	Q96PD2-1

Frequencies

GnomAD3 genomes

AF:

0.0000197

AC:

AN:

152012

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000623

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000158

AC:

AN:

239834

Hom.:

AF XY:

0.000231

AC XY:

AN XY:

130118

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00128

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000659

AC:

AN:

1456762

Hom.:

Cov.:

AF XY:

0.0000980

AC XY:

AN XY:

724192

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00109

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000498

GnomAD4 genome

AF:

0.0000197

AC:

AN:

152130

Hom.:

Cov.:

AF XY:

0.0000403

AC XY:

AN XY:

74380

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000623

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

ExAC

AF:

0.000157

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 07, 2021

The c.1034C>T (p.T345I) alteration is located in exon 8 (coding exon 8) of the DCBLD2 gene. This alteration results from a C to T substitution at nucleotide position 1034, causing the threonine (T) at amino acid position 345 to be replaced by an isoleucine (I). 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

0.28

BayesDel_addAF

Benign

-0.27

BayesDel_noAF

Benign

-0.19

Cadd

Uncertain

Dann

Uncertain

1.0

DEOGEN2

Uncertain

0.47

T;.

Eigen

Benign

0.093

Eigen_PC

Benign

0.15

FATHMM_MKL

Uncertain

0.81

LIST_S2

Benign

0.83

T;T

M_CAP

Benign

0.080

MetaRNN

Benign

0.058

T;T

MetaSVM

Uncertain

-0.16

MutationAssessor

Benign

1.7

L;L

MutationTaster

Benign

0.79

D;D

PrimateAI

Benign

0.44

PROVEAN

Uncertain

-2.7

D;D

REVEL

Uncertain

0.36

Sift

Uncertain

0.024

D;T

Sift4G

Uncertain

0.014

D;D

Polyphen

0.67

P;P

Vest4

0.32

MutPred

0.54

Gain of sheet (P = 0.1208);Gain of sheet (P = 0.1208);

MVP

0.86

MPC

0.23

ClinPred

0.16

GERP RS

4.4

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.11

gMVP

0.32

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over