6-117503949-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001366458.2(DCBLD1):c.295C>G(p.Leu99Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: DCBLD1 NM_001366458.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.99

Genes affected

DCBLD1 (HGNC:21479): (discoidin, CUB and LCCL domain containing 1) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DCBLD1	NM_001366458.2	c.295C>G	p.Leu99Val	missense_variant	2/15	ENST00000338728.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DCBLD1	ENST00000338728.10	c.295C>G	p.Leu99Val	missense_variant	2/15	5	NM_001366458.2	A2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

Bravo AF: 0.0000189

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

Dec 12, 2023

The c.295C>G (p.L99V) alteration is located in exon 2 (coding exon 2) of the DCBLD1 gene. This alteration results from a C to G substitution at nucleotide position 295, causing the leucine (L) at amino acid position 99 to be replaced by a valine (V). 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	0.11
BayesDel_addAF	Benign	-0.10	T
BayesDel_noAF	Benign	-0.38
Cadd	Benign	21
Dann	Uncertain	0.99
Eigen	Benign	0.14
Eigen_PC	Benign	0.11
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Benign	0.71	T;T
M_CAP	Benign	0.018	T
MetaRNN	Uncertain	0.72	D;D
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.3	L;L
MutationTaster	Benign	0.74	D;D;N
PrimateAI	Benign	0.42	T
PROVEAN	Benign	-1.9	N;N
REVEL	Benign	0.21
Sift	Benign	0.038	D;T
Sift4G	Uncertain	0.045	D;T
Polyphen		0.99	D;D
Vest4		0.68
MutPred		0.54		Loss of catalytic residue at L99 (P = 0.0777);Loss of catalytic residue at L99 (P = 0.0777);
MVP		0.32
MPC		0.51
ClinPred		0.78	D
GERP RS		3.4
Varity_R		0.12
gMVP		0.33

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: rs1173427516; hg19: chr6-117825112;