3-98817808-T-C

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_Strong BP6_Moderate BP7 BS1 BS2

The NM_080927.4(DCBLD2):c.1173A>G(p.Lys391=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00261 in 1,613,730 control chromosomes in the GnomAD database, including 99 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.014 (55 hom., cov: 32)
  • Exomes 𝑓: 0.0014 (44 hom.)
• Consequence: DCBLD2 NM_080927.4 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.249

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 -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.64).
• BP6: Variant 3-98817808-T-C is Benign according to our data. Variant chr3-98817808-T-C is described in ClinVar as [Benign]. Clinvar id is 787020.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.249 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0144 (2200/152324) while in subpopulation AFR AF= 0.0507 (2107/41564). AF 95% confidence interval is 0.0489. There are 55 homozygotes in gnomad4. There are 1013 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 55 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DCBLD2	NM_080927.4	c.1173A>G	p.Lys391=	synonymous_variant	9/16	ENST00000326840.11
DCBLD2	XM_011512419.3	c.945A>G	p.Lys315=	synonymous_variant	8/15
DCBLD2	XM_024453348.2	c.855A>G	p.Lys285=	synonymous_variant	9/16

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DCBLD2	ENST00000326840.11	c.1173A>G	p.Lys391=	synonymous_variant	9/16	1	NM_080927.4	P1

Frequencies

GnomAD3 genomes AF: 0.0144 AC: 2195 AN: 152206 Hom.: 55 Cov.: 32

Gnomad AFR AF: 0.0507

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00458

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0000588

Gnomad OTH AF: 0.00860

GnomAD3 exomes AF: 0.00335 AC: 835 AN: 249136 Hom.: 17 AF XY: 0.00237 AC XY: 320 AN XY: 135152

Gnomad AFR exome AF: 0.0499

Gnomad AMR exome AF: 0.00122

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000131

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000620

Gnomad OTH exome AF: 0.00149

GnomAD4 exome AF: 0.00137 AC: 2005 AN: 1461406 Hom.: 44 Cov.: 31 AF XY: 0.00115 AC XY: 839 AN XY: 726998

Gnomad4 AFR exome AF: 0.0511

Gnomad4 AMR exome AF: 0.00175

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000927

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000495

Gnomad4 OTH exome AF: 0.00237

GnomAD4 genome AF: 0.0144 AC: 2200 AN: 152324 Hom.: 55 Cov.: 32 AF XY: 0.0136 AC XY: 1013 AN XY: 74490

Gnomad4 AFR AF: 0.0507

Gnomad4 AMR AF: 0.00458

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000588

Gnomad4 OTH AF: 0.00851

Alfa AF: 0.00861 Hom.: 16

Bravo AF: 0.0166

Asia WGS AF: 0.00231 AC: 8 AN: 3478

EpiCase AF: 0.0000545

EpiControl AF: 0.0000593

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Oct 19, 2017

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.64
Cadd	Benign	6.5
Dann	Benign	0.82
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs116350450; hg19: chr3-98536652;