3-98822272-G-C

Variant names:

• chr3-98822272-G-C
• rs828616
• NM_080927.4:c.786C>G

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_080927.4(DCBLD2):​c.786C>G​(p.Ile262Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: DCBLD2 NM_080927.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.07
• Publications: 21 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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: Splicing predictors support a deleterious effect. Scorers claiming Pathogenic: max_spliceai. No scorers claiming Uncertain. No scorers claiming Benign.

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.786C>G	p.Ile262Met	missense	Exon 6 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.786C>G	p.Ile262Met	missense	Exon 6 of 16	ENSP00000321573.6
	DCBLD2	ENST00000326857.9	TSL:1	c.786C>G	p.Ile262Met	missense	Exon 6 of 16	ENSP00000321646.9
	DCBLD2	ENST00000469648.5	TSL:3	n.*37C>G		downstream_gene	N/A

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 39

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.20
BayesDel_addAF	Uncertain	0.11	D
BayesDel_noAF	Uncertain	-0.080
CADD	Pathogenic	28
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.45	T
Eigen	Uncertain	0.28
Eigen_PC	Uncertain	0.26
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Uncertain	0.87	D
M_CAP	Benign	0.060	D
MetaRNN	Uncertain	0.73	D
MetaSVM	Uncertain	0.33	D
MutationAssessor	Uncertain	2.3	M
PhyloP100		2.1
PrimateAI	Uncertain	0.64	T
PROVEAN	Benign	-1.6	N
REVEL	Uncertain	0.57
Sift	Uncertain	0.010	D
Sift4G	Uncertain	0.017	D
Polyphen		0.97	D
Vest4		0.51
MutPred		0.38		Gain of disorder (P = 0.0828)
MVP		0.92
MPC		0.31
ClinPred		0.95	D
GERP RS		2.8
Varity_R		0.22
gMVP		0.42
Mutation Taster		=68/32	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.72		Details are displayed if max score is > 0.2
DS_DG_spliceai		0.72		Position offset: 5

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs828616; hg19: chr3-98541116;