Variant 3-98901188-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The ENST00000326840.11(DCBLD2):c.139A>G(p.Met47Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00105 in 1,536,966 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0013 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0010 ( 4 hom. )

Consequence

DCBLD2
ENST00000326840.11 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.86

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.009229064).

BS2

High Homozygotes in GnomAdExome4 at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DCBLD2	NM_080927.4 linkuse as main transcript	c.139A>G	p.Met47Val	missense_variant	1/16	ENST00000326840.11	NP_563615.3	Q96PD2-1
DCBLD2	XM_011512419.3 linkuse as main transcript	c.139A>G	p.Met47Val	missense_variant	1/15		XP_011510721.1
DCBLD2	XM_024453348.2 linkuse as main transcript	c.-10910A>G		upstream_gene_variant			XP_024309116.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
DCBLD2	ENST00000326840.11 linkuse as main transcript	c.139A>G	p.Met47Val	missense_variant	1/16	1	NM_080927.4	ENSP00000321573.6	Q96PD2-1
DCBLD2	ENST00000326857.9 linkuse as main transcript	c.139A>G	p.Met47Val	missense_variant	1/16	1		ENSP00000321646.9	Q96PD2-2
DCBLD2	ENST00000449482.1 linkuse as main transcript	c.-245A>G		upstream_gene_variant		1		ENSP00000396803.1	C9JIW6

Frequencies

GnomAD3 genomes

AF:

0.00132

AC:

201

AN:

151996

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000483

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

Gnomad ASJ

AF:

0.000578

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00415

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00224

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000943

AC:

133

AN:

141038

Hom.:

AF XY:

0.000860

AC XY:

AN XY:

75588

show subpopulations

Gnomad AFR exome

AF:

0.000258

Gnomad AMR exome

AF:

0.0000812

Gnomad ASJ exome

AF:

0.000474

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00528

Gnomad NFE exome

AF:

0.00158

Gnomad OTH exome

AF:

0.000938

GnomAD4 exome

AF:

0.00102

AC:

1418

AN:

1384854

Hom.:

Cov.:

AF XY:

0.00108

AC XY:

737

AN XY:

683454

show subpopulations

Gnomad4 AFR exome

AF:

0.0000634

Gnomad4 AMR exome

AF:

0.0000840

Gnomad4 ASJ exome

AF:

0.000397

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00524

Gnomad4 NFE exome

AF:

0.00109

Gnomad4 OTH exome

AF:

0.000691

GnomAD4 genome

AF:

0.00132

AC:

201

AN:

152112

Hom.:

Cov.:

AF XY:

0.00140

AC XY:

104

AN XY:

74380

show subpopulations

Gnomad4 AFR

AF:

0.0000482

Gnomad4 AMR

AF:

0.0000655

Gnomad4 ASJ

AF:

0.000578

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00415

Gnomad4 NFE

AF:

0.00224

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.00148

Hom.:

Bravo

AF:

0.000748

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000936

AC:

ExAC

AF:

0.000635

AC:

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

Aug 17, 2022

The c.139A>G (p.M47V) alteration is located in exon 1 (coding exon 1) of the DCBLD2 gene. This alteration results from a A to G substitution at nucleotide position 139, causing the methionine (M) at amino acid position 47 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

0.071

BayesDel_addAF

Benign

-0.32

BayesDel_noAF

Benign

-0.22

CADD

Benign

DANN

Benign

0.96

DEOGEN2

Benign

0.0014

T;.

Eigen

Benign

-0.45

Eigen_PC

Benign

-0.29

FATHMM_MKL

Uncertain

0.78

LIST_S2

Benign

0.43

T;T

M_CAP

Pathogenic

0.31

MetaRNN

Benign

0.0092

T;T

MetaSVM

Benign

-0.61

MutationAssessor

Benign

0.55

N;N

MutationTaster

Benign

1.0

N;N

PrimateAI

Uncertain

0.70

PROVEAN

Benign

-0.34

N;N

REVEL

Uncertain

0.29

Sift

Benign

0.87

T;T

Sift4G

Benign

0.63

T;T

Polyphen

0.0030

B;B

Vest4

0.33

MVP

0.68

MPC

0.10

ClinPred

0.061

GERP RS

3.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.24

gMVP

0.44

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