chr3-98799686-T-C

Position:

chr3-98799686-T-C

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2

The NM_080927.4(DCBLD2):c.2014A>G(p.Ile672Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00466 in 1,613,996 control chromosomes in the GnomAD database, including 29 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

Frequency

Genomes: 𝑓 0.0031 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0048 ( 29 hom. )

Consequence

DCBLD2
NM_080927.4 missense

Scores

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: -0.308

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 Benign. Variant got -9 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0032678843).

BP6

Variant 3-98799686-T-C is Benign according to our data. Variant chr3-98799686-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 3060115.Status of the report is no_assertion_criteria_provided, 0 stars.

BS2

High Homozygotes in GnomAdExome4 at 29 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
DCBLD2	NM_080927.4 linkuse as main transcript	c.2014A>G	p.Ile672Val	missense_variant	16/16	ENST00000326840.11
DCBLD2	XM_011512419.3 linkuse as main transcript	c.1786A>G	p.Ile596Val	missense_variant	15/15
DCBLD2	XM_024453348.2 linkuse as main transcript	c.1696A>G	p.Ile566Val	missense_variant	16/16

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DCBLD2	ENST00000326840.11 linkuse as main transcript	c.2014A>G	p.Ile672Val	missense_variant	16/16	1	NM_080927.4	P1	Q96PD2-1
DCBLD2	ENST00000326857.9 linkuse as main transcript	c.2056A>G	p.Ile686Val	missense_variant	16/16	1			Q96PD2-2
ST3GAL6	ENST00000491912.1 linkuse as main transcript	n.254-1736T>C		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes

AF:

0.00312

AC:

475

AN:

152196

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00104

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00334

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00122

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00526

Gnomad OTH

AF:

0.00431

GnomAD3 exomes

AF:

0.00288

AC:

716

AN:

248850

Hom.:

AF XY:

0.00299

AC XY:

404

AN XY:

134992

show subpopulations

Gnomad AFR exome

AF:

0.00110

Gnomad AMR exome

AF:

0.00177

Gnomad ASJ exome

AF:

0.000398

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00190

Gnomad NFE exome

AF:

0.00505

Gnomad OTH exome

AF:

0.00380

GnomAD4 exome

AF:

0.00482

AC:

7042

AN:

1461682

Hom.:

Cov.:

AF XY:

0.00470

AC XY:

3418

AN XY:

727122

show subpopulations

Gnomad4 AFR exome

AF:

0.00114

Gnomad4 AMR exome

AF:

0.00210

Gnomad4 ASJ exome

AF:

0.000230

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000232

Gnomad4 FIN exome

AF:

0.00169

Gnomad4 NFE exome

AF:

0.00593

Gnomad4 OTH exome

AF:

0.00363

GnomAD4 genome

AF:

0.00312

AC:

475

AN:

152314

Hom.:

Cov.:

AF XY:

0.00273

AC XY:

203

AN XY:

74486

show subpopulations

Gnomad4 AFR

AF:

0.00103

Gnomad4 AMR

AF:

0.00333

Gnomad4 ASJ

AF:

0.000288

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00122

Gnomad4 NFE

AF:

0.00526

Gnomad4 OTH

AF:

0.00426

Alfa

AF:

0.00422

Hom.:

Bravo

AF:

0.00310

TwinsUK

AF:

0.00647

AC:

ALSPAC

AF:

0.00649

AC:

ESP6500AA

AF:

0.00128

AC:

ESP6500EA

AF:

0.00554

AC:

ExAC

AF:

0.00308

AC:

372

EpiCase

AF:

0.00464

EpiControl

AF:

0.00504

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

DCBLD2-related disorder

Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Feb 25, 2022

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.055

BayesDel_addAF

Benign

-0.71

BayesDel_noAF

Benign

-0.80

CADD

Benign

0.15

DANN

Benign

0.64

DEOGEN2

Benign

0.00085

T;.

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.081

LIST_S2

Benign

0.62

T;T

M_CAP

Benign

0.0060

MetaRNN

Benign

0.0033

T;T

MetaSVM

Benign

-0.99

MutationAssessor

Benign

0.40

N;.

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.24

PROVEAN

Benign

-0.030

N;N

REVEL

Benign

0.0060

Sift

Benign

0.74

T;T

Sift4G

Benign

1.0

T;T

Polyphen

0.0

B;B

Vest4

0.016

MVP

0.085

MPC

0.082

ClinPred

0.000049

GERP RS

-3.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.012

gMVP

0.14

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