3-98817819-C-T

Position:

• chr3-98817819-C-T

Variant summary

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

The NM_080927.4(DCBLD2):​c.1162G>A​(p.Asp388Asn) variant causes a missense change. The variant allele was found at a frequency of 0.00129 in 1,613,708 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.0014 (1 hom., cov: 32)
  • Exomes 𝑓: 0.0013 (2 hom.)
• Consequence: DCBLD2 NM_080927.4 missense
• Clinical Significance: Likely benign no assertion criteria provided B:1
• Conservation: PhyloP100: 7.09

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=0.058354497).
• BP6: Variant 3-98817819-C-T is Benign according to our data. Variant chr3-98817819-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 3038512.Status of the report is no_assertion_criteria_provided, 0 stars.
• BS2: High Homozygotes in GnomAdExome4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DCBLD2	NM_080927.4	c.1162G>A	p.Asp388Asn	missense_variant	9/16	ENST00000326840.11	NP_563615.3
DCBLD2	XM_011512419.3	c.934G>A	p.Asp312Asn	missense_variant	8/15		XP_011510721.1
DCBLD2	XM_024453348.2	c.844G>A	p.Asp282Asn	missense_variant	9/16		XP_024309116.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DCBLD2	ENST00000326840.11	c.1162G>A	p.Asp388Asn	missense_variant	9/16	1	NM_080927.4	ENSP00000321573	P1

Frequencies

GnomAD3 genomes AF: 0.00143 AC: 217 AN: 152220 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00314

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00122

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00206

Gnomad OTH AF: 0.00191

GnomAD3 exomes AF: 0.00131 AC: 326 AN: 249124 Hom.: 1 AF XY: 0.00143 AC XY: 193 AN XY: 135162

Gnomad AFR exome AF: 0.000129

Gnomad AMR exome AF: 0.00168

Gnomad ASJ exome AF: 0.000596

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000327

Gnomad FIN exome AF: 0.000975

Gnomad NFE exome AF: 0.00206

Gnomad OTH exome AF: 0.000827

GnomAD4 exome AF: 0.00128 AC: 1867 AN: 1461370 Hom.: 2 Cov.: 31 AF XY: 0.00132 AC XY: 957 AN XY: 726972

Gnomad4 AFR exome AF: 0.000239

Gnomad4 AMR exome AF: 0.00170

Gnomad4 ASJ exome AF: 0.000612

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000464

Gnomad4 FIN exome AF: 0.000768

Gnomad4 NFE exome AF: 0.00149

Gnomad4 OTH exome AF: 0.000961

GnomAD4 genome AF: 0.00142 AC: 217 AN: 152338 Hom.: 1 Cov.: 32 AF XY: 0.00140 AC XY: 104 AN XY: 74508

Gnomad4 AFR AF: 0.000241

Gnomad4 AMR AF: 0.00314

Gnomad4 ASJ AF: 0.000288

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00122

Gnomad4 NFE AF: 0.00206

Gnomad4 OTH AF: 0.00189

Alfa AF: 0.00169 Hom.: 2

Bravo AF: 0.00131

TwinsUK AF: 0.000809 AC: 3

ALSPAC AF: 0.00234 AC: 9

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.00145 AC: 12

ExAC AF: 0.00150 AC: 181

Asia WGS AF: 0.00144 AC: 5 AN: 3478

EpiCase AF: 0.00256

EpiControl AF: 0.00285

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

Jan 03, 2023

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	0.079
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Uncertain	-0.030
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.32	T;.
Eigen	Uncertain	0.39
Eigen_PC	Uncertain	0.52
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Uncertain	0.87	D;D
M_CAP	Benign	0.080	D
MetaRNN	Benign	0.058	T;T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	1.3	L;L
MutationTaster	Benign	1.0	D;D
PrimateAI	Benign	0.47	T
PROVEAN	Benign	-1.4	N;N
REVEL	Pathogenic	0.65
Sift	Benign	0.50	T;T
Sift4G	Benign	0.28	T;T
Polyphen		1.0	D;P
Vest4		0.87
MVP		0.97
MPC		0.22
ClinPred		0.039	T
GERP RS		5.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.30
gMVP		0.80

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: rs149988957; hg19: chr3-98536663;