Variant 3-98799571-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_080927.4(DCBLD2):c.2129C>T(p.Pro710Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00000684 in 1,461,702 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000068 ( 0 hom. )

Consequence

DCBLD2
NM_080927.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.99

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:):

ST3GAL6 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

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=0.13035023).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DCBLD2	NM_080927.4 linkuse as main transcript	c.2129C>T	p.Pro710Leu	missense_variant	16/16	ENST00000326840.11	NP_563615.3	Q96PD2-1
DCBLD2	XM_011512419.3 linkuse as main transcript	c.1901C>T	p.Pro634Leu	missense_variant	15/15		XP_011510721.1
DCBLD2	XM_024453348.2 linkuse as main transcript	c.1811C>T	p.Pro604Leu	missense_variant	16/16		XP_024309116.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
DCBLD2	ENST00000326840.11 linkuse as main transcript	c.2129C>T	p.Pro710Leu	missense_variant	16/16	1	NM_080927.4	ENSP00000321573.6	Q96PD2-1
DCBLD2	ENST00000326857.9 linkuse as main transcript	c.2171C>T	p.Pro724Leu	missense_variant	16/16	1		ENSP00000321646.9	Q96PD2-2
ST3GAL6	ENST00000491912.1 linkuse as main transcript	n.254-1851G>A		intron_variant		3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000803

AC:

AN:

249174

Hom.:

AF XY:

0.00

AC XY:

AN XY:

135178

show subpopulations

Gnomad AFR exome

AF:

0.00

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:

0.00000684

AC:

AN:

1461702

Hom.:

Cov.:

AF XY:

0.00000688

AC XY:

AN XY:

727132

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000447

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000630

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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

Nov 08, 2024

The c.2129C>T (p.P710L) alteration is located in exon 16 (coding exon 16) of the DCBLD2 gene. This alteration results from a C to T substitution at nucleotide position 2129, causing the proline (P) at amino acid position 710 to be replaced by a leucine (L). 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

0.069

BayesDel_addAF

Benign

-0.28

BayesDel_noAF

Benign

-0.46

CADD

Benign

DANN

Benign

0.63

DEOGEN2

Benign

0.012

T;.

Eigen

Benign

-0.19

Eigen_PC

Benign

-0.19

FATHMM_MKL

Benign

0.59

LIST_S2

Uncertain

0.87

D;D

M_CAP

Benign

0.0071

MetaRNN

Benign

0.13

T;T

MetaSVM

Benign

-0.98

MutationAssessor

Benign

1.6

L;.

PrimateAI

Benign

0.26

PROVEAN

Benign

-2.2

N;N

REVEL

Benign

0.068

Sift

Benign

0.032

D;D

Sift4G

Uncertain

0.017

D;D

Polyphen

0.34

B;B

Vest4

0.22

MutPred

0.35

Gain of sheet (P = 0.0049);.;

MVP

0.40

MPC

0.12

ClinPred

0.13

GERP RS

5.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.032

gMVP

0.31

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