2-164694682-C-T

Variant names:

• chr2-164694682-C-T
• NM_001365672.2:c.2710G>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001365672.2(COBLL1):​c.2710G>A​(p.Ala904Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,714 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 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: 6.8e-7 (0 hom.)
• Consequence: COBLL1 NM_001365672.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.215
• Publications: 0 publications found

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

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.035786003).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001365672.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	COBLL1	NM_001365672.2	MANE Select	c.2710G>A	p.Ala904Thr	missense	Exon 12 of 14	NP_001352601.1	Q53SF7-4
	COBLL1	NM_001278458.2		c.3025G>A	p.Ala1009Thr	missense	Exon 15 of 17	NP_001265387.1	A0A0D9SG04
	COBLL1	NM_001278460.2		c.2848G>A	p.Ala950Thr	missense	Exon 12 of 14	NP_001265389.1	A0A0X1KG75

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	COBLL1	ENST00000652658.2	MANE Select	c.2710G>A	p.Ala904Thr	missense	Exon 12 of 14	ENSP00000498242.1	Q53SF7-4
	COBLL1	ENST00000409184.8	TSL:1	c.2848G>A	p.Ala950Thr	missense	Exon 12 of 14	ENSP00000387326.5	A0A0X1KG75
	COBLL1	ENST00000342193.8	TSL:1	c.2824G>A	p.Ala942Thr	missense	Exon 12 of 14	ENSP00000341360.4	Q53SF7-3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461714 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 727154

African (AFR) AF: 0.00 AC: 0 AN: 33468

American (AMR) AF: 0.00 AC: 0 AN: 44670

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26126

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.00 AC: 0 AN: 86256

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53396

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5762

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1111952

Other (OTH) AF: 0.00 AC: 0 AN: 60386

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.068
BayesDel_addAF	Benign	-0.29	T
BayesDel_noAF	Benign	-0.65
CADD	Benign	0.47
DANN	Benign	0.82
DEOGEN2	Benign	0.0020	T
Eigen	Benign	-0.99
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.049	N
LIST_S2	Benign	0.54	T
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.036	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.90	L
PhyloP100		-0.21
PrimateAI	Benign	0.22	T
PROVEAN	Benign	-0.88	N
REVEL	Benign	0.039
Sift	Benign	0.19	T
Sift4G	Benign	0.16	T
Polyphen		0.18	B
Vest4		0.029
MutPred		0.089		Gain of phosphorylation at A980 (P = 0.0077)
MVP		0.17
MPC		0.061
ClinPred		0.043	T
GERP RS		0.58
Varity_R		0.038
gMVP		0.18
Mutation Taster		=99/1	polymorphism

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

Other links and lift over

hg19: chr2-165551192;