Variant chr2-164695372-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001365672.2(COBLL1):c.2020A>G(p.Lys674Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,748 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 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)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

COBLL1
NM_001365672.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.995

Variant links:

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]

COBLL1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

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=0.17740306).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
COBLL1	NM_001365672.2 linkuse as main transcript	c.2020A>G	p.Lys674Glu	missense_variant	12/14	ENST00000652658.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
COBLL1	ENST00000652658.2 linkuse as main transcript	c.2020A>G	p.Lys674Glu	missense_variant	12/14		NM_001365672.2	A2	Q53SF7-4

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000398

AC:

AN:

251188

Hom.:

AF XY:

0.00

AC XY:

AN XY:

135744

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000881

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1461748

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727172

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000180

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 05, 2023

The c.2134A>G (p.K712E) alteration is located in exon 12 (coding exon 12) of the COBLL1 gene. This alteration results from a A to G substitution at nucleotide position 2134, causing the lysine (K) at amino acid position 712 to be replaced by a glutamic acid (E). 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

0.094

BayesDel_addAF

Benign

-0.067

BayesDel_noAF

Benign

-0.33

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.024

T;.;.;T

Eigen

Benign

-0.40

Eigen_PC

Benign

-0.28

FATHMM_MKL

Uncertain

0.79

LIST_S2

Benign

0.73

T;T;T;T

M_CAP

Benign

0.0063

MetaRNN

Benign

0.18

T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.6

L;.;.;.

MutationTaster

Benign

0.96

N;N;N;N;N

PrimateAI

Benign

0.38

PROVEAN

Benign

-1.7

N;N;N;.

REVEL

Benign

0.18

Sift

Benign

0.11

T;T;T;.

Sift4G

Benign

0.18

T;T;T;T

Polyphen

0.073

B;.;.;.

Vest4

0.32

MutPred

0.28

Loss of methylation at K750 (P = 0.0045);.;.;.;

MVP

0.47

MPC

0.084

ClinPred

0.11

GERP RS

4.9

Varity_R

0.099

gMVP

0.45

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over