chr2-164694432-G-A

Position:

• chr2-164694432-G-A

Variant summary

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

The NM_001365672.2(COBLL1):​c.2960C>T​(p.Pro987Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00000205 in 1,461,726 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: COBLL1 NM_001365672.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.07

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/exons	MANE	Protein	UniProt
COBLL1	NM_001365672.2	c.2960C>T	p.Pro987Leu	missense_variant	12/14	ENST00000652658.2	NP_001352601.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
COBLL1	ENST00000652658.2	c.2960C>T	p.Pro987Leu	missense_variant	12/14		NM_001365672.2	ENSP00000498242.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000205 AC: 3 AN: 1461726 Hom.: 0 Cov.: 32 AF XY: 0.00000275 AC XY: 2 AN XY: 727162

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: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

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

Jun 08, 2022

The c.3074C>T (p.P1025L) alteration is located in exon 12 (coding exon 12) of the COBLL1 gene. This alteration results from a C to T substitution at nucleotide position 3074, causing the proline (P) at amino acid position 1025 to be replaced by a leucine (L). 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	Uncertain	0.42
BayesDel_addAF	Pathogenic	0.22	D
BayesDel_noAF	Uncertain	0.080
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.26	T;.;.;T
Eigen	Uncertain	0.57
Eigen_PC	Uncertain	0.50
FATHMM_MKL	Benign	0.68	D
LIST_S2	Uncertain	0.92	D;D;D;D
M_CAP	Benign	0.0094	T
MetaRNN	Uncertain	0.49	T;T;T;T
MetaSVM	Benign	-0.29	T
MutationAssessor	Uncertain	2.6	M;.;.;.
PrimateAI	Uncertain	0.74	T
PROVEAN	Pathogenic	-5.8	D;D;D;.
REVEL	Uncertain	0.29
Sift	Uncertain	0.0020	D;D;D;.
Sift4G	Uncertain	0.019	D;D;D;D
Polyphen		1.0	D;.;.;.
Vest4		0.61
MutPred		0.36		Loss of glycosylation at P1063 (P = 0.0272);.;.;.;
MVP		0.63
MPC		0.34
ClinPred		0.99	D
GERP RS		5.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.35
gMVP		0.27

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: chr2-165550942;