rs16840208

Variant names:

• chr3-98799533-C-T
• rs16840208
• NM_080927.4:c.2167G>A

Variant summary

Our verdict is Benign. The variant received -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.

• 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
• Publications: 13 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_080927.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DCBLD2	NM_080927.4	MANE Select	c.2167G>A	p.Asp723Asn	missense	Exon 16 of 16	NP_563615.3

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DCBLD2	ENST00000326840.11	TSL:1 MANE Select	c.2167G>A	p.Asp723Asn	missense	Exon 16 of 16	ENSP00000321573.6
	DCBLD2	ENST00000326857.9	TSL:1	c.2209G>A	p.Asp737Asn	missense	Exon 16 of 16	ENSP00000321646.9
	ST3GAL6	ENST00000491912.1	TSL:3	n.254-1889C>T		intron	N/A

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

GnomAD2 exomes AF: 0.0208 AC: 5184 AN: 249042 AF XY: 0.0167

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 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

African (AFR) AF: 0.00212 AC: 71 AN: 33478

American (AMR) AF: 0.0851 AC: 3804 AN: 44718

Ashkenazi Jewish (ASJ) AF: 0.00145 AC: 38 AN: 26136

East Asian (EAS) AF: 0.0537 AC: 2130 AN: 39700

South Asian (SAS) AF: 0.00209 AC: 180 AN: 86258

European-Finnish (FIN) AF: 0.0271 AC: 1447 AN: 53402

Middle Eastern (MID) AF: 0.000867 AC: 5 AN: 5768

European-Non Finnish (NFE) AF: 0.000468 AC: 520 AN: 1111860

Other (OTH) AF: 0.00990 AC: 598 AN: 60374

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

African (AFR) AF: 0.00356 AC: 148 AN: 41556

American (AMR) AF: 0.0640 AC: 979 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.00259 AC: 9 AN: 3472

East Asian (EAS) AF: 0.0631 AC: 326 AN: 5170

South Asian (SAS) AF: 0.00352 AC: 17 AN: 4826

European-Finnish (FIN) AF: 0.0291 AC: 309 AN: 10618

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00112 AC: 76 AN: 68018

Other (OTH) AF: 0.0203 AC: 43 AN: 2114

Alfa AF: 0.00500 Hom.: 35

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 v4.9

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
MetaRNN	Benign	0.0017	T
MetaSVM	Benign	-0.84	T
MutationAssessor	Uncertain	2.7	M
PhyloP100		5.3
PrimateAI	Uncertain	0.50	T
PROVEAN	Benign	-2.0	N
REVEL	Benign	0.17
Sift	Uncertain	0.023	D
Sift4G	Benign	0.064	T
Polyphen		0.0030	B
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
Mutation Taster		=95/5	polymorphism (auto)

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

Other links and lift over

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