rs16840208

Positions:

• chr3-98799533-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_080927.4(DCBLD2):​c.2167G>A​(p.Asp723Asn) variant causes a missense change. The variant allele was found at a frequency of 0.00663 in 1,613,970 control chromosomes in the GnomAD database, including 345 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.013 (59 hom., cov: 32)
  • Exomes 𝑓: 0.0060 (286 hom.)
• Consequence: DCBLD2 NM_080927.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.28

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0017092526).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0607 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DCBLD2	NM_080927.4	c.2167G>A	p.Asp723Asn	missense_variant	16/16	ENST00000326840.11	NP_563615.3
DCBLD2	XM_011512419.3	c.1939G>A	p.Asp647Asn	missense_variant	15/15		XP_011510721.1
DCBLD2	XM_024453348.2	c.1849G>A	p.Asp617Asn	missense_variant	16/16		XP_024309116.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DCBLD2	ENST00000326840.11	c.2167G>A	p.Asp723Asn	missense_variant	16/16	1	NM_080927.4	ENSP00000321573	P1
DCBLD2	ENST00000326857.9	c.2209G>A	p.Asp737Asn	missense_variant	16/16	1		ENSP00000321646
ST3GAL6	ENST00000491912.1	n.254-1889C>T		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.0125 AC: 1897 AN: 152158 Hom.: 56 Cov.: 32

Gnomad AFR AF: 0.00357

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0635

Gnomad ASJ AF: 0.00259

Gnomad EAS AF: 0.0629

Gnomad SAS AF: 0.00352

Gnomad FIN AF: 0.0291

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00112

Gnomad OTH AF: 0.0201

GnomAD3 exomes AF: 0.0208 AC: 5184 AN: 249042 Hom.: 213 AF XY: 0.0167 AC XY: 2258 AN XY: 135096

Gnomad AFR exome AF: 0.00413

Gnomad AMR exome AF: 0.0899

Gnomad ASJ exome AF: 0.00169

Gnomad EAS exome AF: 0.0613

Gnomad SAS exome AF: 0.00173

Gnomad FIN exome AF: 0.0289

Gnomad NFE exome AF: 0.00127

Gnomad OTH exome AF: 0.0129

GnomAD4 exome AF: 0.00602 AC: 8793 AN: 1461694 Hom.: 286 Cov.: 32 AF XY: 0.00540 AC XY: 3930 AN XY: 727128

Gnomad4 AFR exome AF: 0.00212

Gnomad4 AMR exome AF: 0.0851

Gnomad4 ASJ exome AF: 0.00145

Gnomad4 EAS exome AF: 0.0537

Gnomad4 SAS exome AF: 0.00209

Gnomad4 FIN exome AF: 0.0271

Gnomad4 NFE exome AF: 0.000468

Gnomad4 OTH exome AF: 0.00990

GnomAD4 genome AF: 0.0125 AC: 1907 AN: 152276 Hom.: 59 Cov.: 32 AF XY: 0.0149 AC XY: 1112 AN XY: 74452

Gnomad4 AFR AF: 0.00356

Gnomad4 AMR AF: 0.0640

Gnomad4 ASJ AF: 0.00259

Gnomad4 EAS AF: 0.0631

Gnomad4 SAS AF: 0.00352

Gnomad4 FIN AF: 0.0291

Gnomad4 NFE AF: 0.00112

Gnomad4 OTH AF: 0.0203

Alfa AF: 0.00368 Hom.: 17

Bravo AF: 0.0153

TwinsUK AF: 0.000270 AC: 1

ALSPAC AF: 0.00182 AC: 7

ESP6500AA AF: 0.00354 AC: 14

ESP6500EA AF: 0.000841 AC: 7

ExAC AF: 0.0164 AC: 1982

Asia WGS AF: 0.0440 AC: 153 AN: 3478

EpiCase AF: 0.000600

EpiControl AF: 0.000593

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.077
BayesDel_addAF	Benign	-0.56	T
BayesDel_noAF	Benign	-0.51
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.012	T;.
Eigen	Benign	0.14
Eigen_PC	Benign	0.21
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Benign	0.81	T;T
MetaRNN	Benign	0.0017	T;T
MetaSVM	Benign	-0.84	T
MutationAssessor	Uncertain	2.7	M;.
MutationTaster	Benign	1.0	D;D
PrimateAI	Uncertain	0.50	T
PROVEAN	Benign	-2.0	N;N
REVEL	Benign	0.17
Sift	Uncertain	0.023	D;D
Sift4G	Benign	0.064	T;T
Polyphen		0.0030	B;D
Vest4		0.10
MPC		0.39
ClinPred		0.037	T
GERP RS		4.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.081
gMVP		0.48

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: rs16840208; hg19: chr3-98518377; COSMIC: COSV54585896; COSMIC: COSV54585896;