2-164694655-C-G

Variant names:

• chr2-164694655-C-G
• NM_001365672.2:c.2737G>C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001365672.2(COBLL1):​c.2737G>C​(p.Glu913Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/20 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: COBLL1 NM_001365672.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.78

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.17405471).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COBLL1	NM_001365672.2	c.2737G>C	p.Glu913Gln	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.2737G>C	p.Glu913Gln	missense_variant	Exon 12 of 14		NM_001365672.2	ENSP00000498242.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Mar 07, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.2851G>C (p.E951Q) alteration is located in exon 12 (coding exon 12) of the COBLL1 gene. This alteration results from a G to C substitution at nucleotide position 2851, causing the glutamic acid (E) at amino acid position 951 to be replaced by a glutamine (Q). 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	0.087
BayesDel_addAF	Benign	-0.056	T
BayesDel_noAF	Benign	-0.32
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Benign	0.022	T;.;.;T
Eigen	Uncertain	0.22
Eigen_PC	Benign	0.095
FATHMM_MKL	Benign	0.53	D
LIST_S2	Benign	0.82	T;T;T;T
M_CAP	Benign	0.0059	T
MetaRNN	Benign	0.17	T;T;T;T
MetaSVM	Benign	-0.92	T
MutationAssessor	Uncertain	2.3	M;.;.;.
PrimateAI	Benign	0.28	T
PROVEAN	Benign	-1.5	N;N;N;.
REVEL	Benign	0.20
Sift	Uncertain	0.016	D;T;D;.
Sift4G	Benign	0.36	T;T;T;T
Polyphen		1.0	D;.;.;.
Vest4		0.062
MutPred		0.12		Loss of phosphorylation at S987 (P = 0.1298);.;.;.;
MVP		0.55
MPC		0.098
ClinPred		0.72	D
GERP RS		4.7
Varity_R		0.14
gMVP		0.17

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr2-165551165;