rs1822017

chr3-98800637-G-A

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_080927.4(DCBLD2):c.1800C>T(p.Ser600=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.157 in 1,613,578 control chromosomes in the GnomAD database, including 20,568 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 0.17 (2463 hom., cov: 32)
  • Exomes 𝑓: 0.15 (18105 hom.)
• Consequence: DCBLD2 NM_080927.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0240

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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.49).
• BP7: Synonymous conserved (PhyloP=0.024 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.245 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DCBLD2	NM_080927.4	c.1800C>T	p.Ser600=	synonymous_variant	15/16	ENST00000326840.11
DCBLD2	XM_011512419.3	c.1572C>T	p.Ser524=	synonymous_variant	14/15
DCBLD2	XM_024453348.2	c.1482C>T	p.Ser494=	synonymous_variant	15/16

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DCBLD2	ENST00000326840.11	c.1800C>T	p.Ser600=	synonymous_variant	15/16	1	NM_080927.4	P1
DCBLD2	ENST00000326857.9	c.1842C>T	p.Ser614=	synonymous_variant	15/16	1
DCBLD2	ENST00000496736.1	n.452C>T		non_coding_transcript_exon_variant	2/3	3
ST3GAL6	ENST00000491912.1	n.254-785G>A		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.174 AC: 26411 AN: 151888 Hom.: 2461 Cov.: 32

Gnomad AFR AF: 0.249

Gnomad AMI AF: 0.270

Gnomad AMR AF: 0.126

Gnomad ASJ AF: 0.196

Gnomad EAS AF: 0.0468

Gnomad SAS AF: 0.179

Gnomad FIN AF: 0.127

Gnomad MID AF: 0.203

Gnomad NFE AF: 0.153

Gnomad OTH AF: 0.151

GnomAD3 exomes AF: 0.145 AC: 36048 AN: 249084 Hom.: 2990 AF XY: 0.147 AC XY: 19927 AN XY: 135126

Gnomad AFR exome AF: 0.250

Gnomad AMR exome AF: 0.0776

Gnomad ASJ exome AF: 0.185

Gnomad EAS exome AF: 0.0431

Gnomad SAS exome AF: 0.181

Gnomad FIN exome AF: 0.122

Gnomad NFE exome AF: 0.158

Gnomad OTH exome AF: 0.149

GnomAD4 exome AF: 0.155 AC: 226143 AN: 1461574 Hom.: 18105 Cov.: 32 AF XY: 0.156 AC XY: 113267 AN XY: 727078

Gnomad4 AFR exome AF: 0.246

Gnomad4 AMR exome AF: 0.0839

Gnomad4 ASJ exome AF: 0.190

Gnomad4 EAS exome AF: 0.0642

Gnomad4 SAS exome AF: 0.180

Gnomad4 FIN exome AF: 0.126

Gnomad4 NFE exome AF: 0.157

Gnomad4 OTH exome AF: 0.150

GnomAD4 genome AF: 0.174 AC: 26413 AN: 152004 Hom.: 2463 Cov.: 32 AF XY: 0.172 AC XY: 12766 AN XY: 74304

Gnomad4 AFR AF: 0.249

Gnomad4 AMR AF: 0.126

Gnomad4 ASJ AF: 0.196

Gnomad4 EAS AF: 0.0467

Gnomad4 SAS AF: 0.178

Gnomad4 FIN AF: 0.127

Gnomad4 NFE AF: 0.153

Gnomad4 OTH AF: 0.151

Alfa AF: 0.164 Hom.: 2719

Bravo AF: 0.176

Asia WGS AF: 0.130 AC: 454 AN: 3478

EpiCase AF: 0.161

EpiControl AF: 0.162

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.49
Cadd	Benign	3.3
Dann	Benign	0.82

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: rs1822017; hg19: chr3-98519481; COSMIC: COSV54578801; COSMIC: COSV54578801;