3-98811485-G-A

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_Strong

The NM_080927.4(DCBLD2):c.1433C>T(p.Pro478Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00132 in 1,613,572 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0011 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0013 (2 hom.)
• Consequence: DCBLD2 NM_080927.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.0470

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 Likely_benign. Variant got -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.008757412).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DCBLD2	NM_080927.4	c.1433C>T	p.Pro478Leu	missense_variant	11/16	ENST00000326840.11
DCBLD2	XM_011512419.3	c.1205C>T	p.Pro402Leu	missense_variant	10/15
DCBLD2	XM_024453348.2	c.1115C>T	p.Pro372Leu	missense_variant	11/16

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DCBLD2	ENST00000326840.11	c.1433C>T	p.Pro478Leu	missense_variant	11/16	1	NM_080927.4	P1

Frequencies

GnomAD3 genomes AF: 0.00107 AC: 163 AN: 152186 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.000217

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000916

Gnomad ASJ AF: 0.00576

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.000283

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00165

Gnomad OTH AF: 0.00143

GnomAD3 exomes AF: 0.00101 AC: 251 AN: 248900 Hom.: 0 AF XY: 0.00104 AC XY: 140 AN XY: 135046

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000349

Gnomad ASJ exome AF: 0.00447

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000164

Gnomad FIN exome AF: 0.000743

Gnomad NFE exome AF: 0.00144

Gnomad OTH exome AF: 0.00166

GnomAD4 exome AF: 0.00134 AC: 1959 AN: 1461268 Hom.: 2 Cov.: 31 AF XY: 0.00131 AC XY: 953 AN XY: 726930

Gnomad4 AFR exome AF: 0.000179

Gnomad4 AMR exome AF: 0.000291

Gnomad4 ASJ exome AF: 0.00452

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000244

Gnomad4 FIN exome AF: 0.000730

Gnomad4 NFE exome AF: 0.00151

Gnomad4 OTH exome AF: 0.00129

GnomAD4 genome AF: 0.00107 AC: 163 AN: 152304 Hom.: 0 Cov.: 33 AF XY: 0.000832 AC XY: 62 AN XY: 74476

Gnomad4 AFR AF: 0.000217

Gnomad4 AMR AF: 0.000915

Gnomad4 ASJ AF: 0.00576

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000414

Gnomad4 FIN AF: 0.000283

Gnomad4 NFE AF: 0.00165

Gnomad4 OTH AF: 0.00142

Alfa AF: 0.00123 Hom.: 0

Bravo AF: 0.000892

TwinsUK AF: 0.00108 AC: 4

ALSPAC AF: 0.000519 AC: 2

ESP6500AA AF: 0.000272 AC: 1

ESP6500EA AF: 0.00208 AC: 17

ExAC AF: 0.000927 AC: 112

EpiCase AF: 0.00191

EpiControl AF: 0.00172

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 20, 2021

The c.1433C>T (p.P478L) alteration is located in exon 11 (coding exon 11) of the DCBLD2 gene. This alteration results from a C to T substitution at nucleotide position 1433, causing the proline (P) at amino acid position 478 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.061
BayesDel_addAF	Benign	-0.37	T
BayesDel_noAF	Benign	-0.34
Cadd	Benign	17
Dann	Benign	0.75
DEOGEN2	Benign	0.0054	T;.
Eigen	Benign	-0.65
Eigen_PC	Benign	-0.56
FATHMM_MKL	Benign	0.37	N
LIST_S2	Benign	0.69	T;T
M_CAP	Benign	0.037	D
MetaRNN	Benign	0.0088	T;T
MetaSVM	Benign	-0.49	T
MutationAssessor	Benign	1.4	L;L
MutationTaster	Benign	1.0	D;D
PrimateAI	Benign	0.30	T
PROVEAN	Benign	-1.7	N;N
REVEL	Benign	0.12
Sift	Benign	0.033	D;D
Sift4G	Benign	0.28	T;T
Polyphen		0.0	B;B
Vest4		0.13
MVP		0.87
MPC		0.10
ClinPred		0.015	T
GERP RS		3.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.031
gMVP		0.59

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: rs200621366; hg19: chr3-98530329;