chr3-98799686-T-C

Position:

• chr3-98799686-T-C

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_Strong BP6 BS2

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
• Clinical Significance: Likely benign no assertion criteria provided B:1
• Conservation: PhyloP100: -0.308

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]

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]

ACMG classification

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	Protein	UniProt
DCBLD2	NM_080927.4	c.2014A>G	p.Ile672Val	missense_variant	16/16	ENST00000326840.11	NP_563615.3
DCBLD2	XM_011512419.3	c.1786A>G	p.Ile596Val	missense_variant	15/15		XP_011510721.1
DCBLD2	XM_024453348.2	c.1696A>G	p.Ile566Val	missense_variant	16/16		XP_024309116.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DCBLD2	ENST00000326840.11	c.2014A>G	p.Ile672Val	missense_variant	16/16	1	NM_080927.4	ENSP00000321573	P1
DCBLD2	ENST00000326857.9	c.2056A>G	p.Ile686Val	missense_variant	16/16	1		ENSP00000321646
ST3GAL6	ENST00000491912.1	n.254-1736T>C		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.00312 AC: 475 AN: 152196 Hom.: 0 Cov.: 32

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.: 4 AF XY: 0.00299 AC XY: 404 AN XY: 134992

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.: 29 Cov.: 32 AF XY: 0.00470 AC XY: 3418 AN XY: 727122

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.: 0 Cov.: 32 AF XY: 0.00273 AC XY: 203 AN XY: 74486

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.: 6

Bravo AF: 0.00310

TwinsUK AF: 0.00647 AC: 24

ALSPAC AF: 0.00649 AC: 25

ESP6500AA AF: 0.00128 AC: 5

ESP6500EA AF: 0.00554 AC: 46

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

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	T
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	N
LIST_S2	Benign	0.62	T;T
M_CAP	Benign	0.0060	T
MetaRNN	Benign	0.0033	T;T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	0.40	N;.
MutationTaster	Benign	1.0	N;N
PrimateAI	Benign	0.24	T
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	T
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

Other links and lift over

dbSNP: rs111245657; hg19: chr3-98518530; COSMIC: COSV105023940; COSMIC: COSV105023940;