3-98799515-G-T

Position:

chr3-98799515-G-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_080927.4(DCBLD2):c.2185C>A(p.Gln729Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000694 in 1,613,978 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00033 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000042 ( 0 hom. )

Consequence

DCBLD2
NM_080927.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.56

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 -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.015273392).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
DCBLD2	NM_080927.4 linkuse as main transcript	c.2185C>A	p.Gln729Lys	missense_variant	16/16	ENST00000326840.11
DCBLD2	XM_011512419.3 linkuse as main transcript	c.1957C>A	p.Gln653Lys	missense_variant	15/15
DCBLD2	XM_024453348.2 linkuse as main transcript	c.1867C>A	p.Gln623Lys	missense_variant	16/16

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DCBLD2	ENST00000326840.11 linkuse as main transcript	c.2185C>A	p.Gln729Lys	missense_variant	16/16	1	NM_080927.4	P1	Q96PD2-1
DCBLD2	ENST00000326857.9 linkuse as main transcript	c.2227C>A	p.Gln743Lys	missense_variant	16/16	1			Q96PD2-2
ST3GAL6	ENST00000491912.1 linkuse as main transcript	n.254-1907G>T		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes

AF:

0.000329

AC:

AN:

152158

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00121

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000723

AC:

AN:

249046

Hom.:

AF XY:

0.0000518

AC XY:

AN XY:

135098

show subpopulations

Gnomad AFR exome

AF:

0.00103

Gnomad AMR exome

AF:

0.0000579

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000424

AC:

AN:

1461702

Hom.:

Cov.:

AF XY:

0.0000344

AC XY:

AN XY:

727132

show subpopulations

Gnomad4 AFR exome

AF:

0.00155

Gnomad4 AMR exome

AF:

0.0000447

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:

0.00

Gnomad4 OTH exome

AF:

0.000133

GnomAD4 genome

AF:

0.000328

AC:

AN:

152276

Hom.:

Cov.:

AF XY:

0.000322

AC XY:

AN XY:

74466

show subpopulations

Gnomad4 AFR

AF:

0.00120

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000151

Hom.:

Bravo

AF:

0.000457

ESP6500AA

AF:

0.00153

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000744

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

Dec 19, 2022

The c.2185C>A (p.Q729K) alteration is located in exon 16 (coding exon 16) of the DCBLD2 gene. This alteration results from a C to A substitution at nucleotide position 2185, causing the glutamine (Q) at amino acid position 729 to be replaced by a lysine (K). 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

0.074

BayesDel_addAF

Benign

-0.56

BayesDel_noAF

Benign

-0.63

CADD

Benign

DANN

Benign

0.95

DEOGEN2

Benign

0.0044

T;.

Eigen

Benign

-0.081

Eigen_PC

Benign

0.089

FATHMM_MKL

Uncertain

0.77

LIST_S2

Benign

0.78

T;T

M_CAP

Benign

0.0042

MetaRNN

Benign

0.015

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.6

L;.

MutationTaster

Benign

0.66

N;N

PrimateAI

Benign

0.21

PROVEAN

Benign

-0.82

N;N

REVEL

Benign

0.065

Sift

Benign

0.35

T;T

Sift4G

Benign

0.29

T;T

Polyphen

0.0090

B;B

Vest4

0.076

MVP

0.23

MPC

0.13

ClinPred

0.046

GERP RS

5.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.13

gMVP

0.26

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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