20-62391310-A-C

Position:

• chr20-62391310-A-C

Variant summary

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

The NM_031215.3(CABLES2):​c.1235T>G​(p.Val412Gly) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: CABLES2 NM_031215.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 9.11

Genes affected

CABLES2 (HGNC:16143): (Cdk5 and Abl enzyme substrate 2) Predicted to be involved in cell division and regulation of cell cycle. [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
CABLES2	NM_031215.3	c.1235T>G	p.Val412Gly	missense_variant	9/10	ENST00000279101.10	NP_112492.2
CABLES2	XM_047440530.1	c.659T>G	p.Val220Gly	missense_variant	7/8		XP_047296486.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CABLES2	ENST00000279101.10	c.1235T>G	p.Val412Gly	missense_variant	9/10	5	NM_031215.3	ENSP00000279101	P1
CABLES2	ENST00000453274.1	c.617T>G	p.Val206Gly	missense_variant	6/7	5		ENSP00000398535

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 36

GnomAD4 genome Cov.: 33

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

Dec 08, 2023

The c.1235T>G (p.V412G) alteration is located in exon 9 (coding exon 9) of the CABLES2 gene. This alteration results from a T to G substitution at nucleotide position 1235, causing the valine (V) at amino acid position 412 to be replaced by a glycine (G). 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	Pathogenic	0.92
BayesDel_addAF	Pathogenic	0.22	D
BayesDel_noAF	Uncertain	0.070
CADD	Pathogenic	28
DANN	Uncertain	1.0
DEOGEN2	Benign	0.19	T
Eigen	Pathogenic	0.78
Eigen_PC	Pathogenic	0.77
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.95	D
M_CAP	Uncertain	0.086	D
MetaRNN	Uncertain	0.74	D
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.0	M
MutationTaster	Benign	1.0	D
PrimateAI	Uncertain	0.79	T
PROVEAN	Pathogenic	-6.2	D
REVEL	Uncertain	0.60
Sift	Uncertain	0.0010	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.62
MutPred		0.58		Gain of helix (P = 0.0425);
MVP		0.89
MPC		1.5
ClinPred		1.0	D
GERP RS		5.6
Varity_R		0.94
gMVP		0.84

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: chr20-60966366;