2-164694771-C-T

Variant names:

• chr2-164694771-C-T
• rs199845314
• NM_001365672.2:c.2621G>A

Variant summary

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

The NM_001365672.2(COBLL1):​c.2621G>A​(p.Arg874Lys) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R874T) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: COBLL1 NM_001365672.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.94

Genes affected

COBLL1 (HGNC:23571): (cordon-bleu WH2 repeat protein like 1) Enables cadherin binding activity. Located in extracellular exosome. [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 rank	MANE	Protein	UniProt
COBLL1	NM_001365672.2	c.2621G>A	p.Arg874Lys	missense_variant	Exon 12 of 14	ENST00000652658.2	NP_001352601.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
COBLL1	ENST00000652658.2	c.2621G>A	p.Arg874Lys	missense_variant	Exon 12 of 14		NM_001365672.2	ENSP00000498242.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.49
BayesDel_addAF	Uncertain	0.028	T
BayesDel_noAF	Benign	-0.20
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.061	T;.;.;T
Eigen	Pathogenic	0.71
Eigen_PC	Pathogenic	0.72
FATHMM_MKL	Uncertain	0.85	D
LIST_S2	Uncertain	0.88	D;D;D;D
M_CAP	Benign	0.0089	T
MetaRNN	Uncertain	0.74	D;D;D;D
MetaSVM	Benign	-0.43	T
MutationAssessor	Uncertain	2.6	M;.;.;.
PrimateAI	Uncertain	0.52	T
PROVEAN	Benign	-2.0	N;N;N;.
REVEL	Benign	0.25
Sift	Benign	0.091	T;T;T;.
Sift4G	Benign	0.20	T;D;T;T
Polyphen		0.99	D;.;.;.
Vest4		0.85
MutPred		0.32		Gain of methylation at R950 (P = 0.0071);.;.;.;
MVP		0.59
MPC		0.34
ClinPred		0.97	D
GERP RS		6.0
Varity_R		0.27
gMVP		0.35

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs199845314; hg19: chr2-165551281;