Variant 20-62393485-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_031215.3(CABLES2):c.835C>T(p.His279Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000171 in 1,460,842 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.000017 ( 0 hom. )

Consequence

CABLES2
NM_031215.3 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.00

Variant links:

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]

CABLES2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.023945004).

BP6

Variant 20-62393485-G-A is Benign according to our data. Variant chr20-62393485-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 3136243.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CABLES2	NM_031215.3 linkuse as main transcript	c.835C>T	p.His279Tyr	missense_variant	6/10	ENST00000279101.10	NP_112492.2
CABLES2	XM_047440530.1 linkuse as main transcript	c.259C>T	p.His87Tyr	missense_variant	4/8		XP_047296486.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CABLES2	ENST00000279101.10 linkuse as main transcript	c.835C>T	p.His279Tyr	missense_variant	6/10	5	NM_031215.3	ENSP00000279101	P1
CABLES2	ENST00000453274.1 linkuse as main transcript	c.217C>T	p.His73Tyr	missense_variant	3/7	5		ENSP00000398535

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000320

AC:

AN:

250246

Hom.:

AF XY:

0.0000369

AC XY:

AN XY:

135330

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:

0.000263

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000171

AC:

AN:

1460842

Hom.:

Cov.:

AF XY:

0.0000234

AC XY:

AN XY:

726690

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:

0.000267

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000180

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.0000330

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 07, 2024

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.058

BayesDel_addAF

Benign

-0.43

BayesDel_noAF

Benign

-0.56

CADD

Benign

7.8

DANN

Benign

0.60

DEOGEN2

Benign

0.0035

Eigen

Benign

-1.1

Eigen_PC

Benign

-0.97

FATHMM_MKL

Benign

0.44

LIST_S2

Benign

0.73

M_CAP

Benign

0.010

MetaRNN

Benign

0.024

MetaSVM

Benign

-0.98

MutationAssessor

Benign

-0.64

MutationTaster

Benign

1.0

PrimateAI

Benign

0.36

PROVEAN

Benign

0.38

REVEL

Benign

0.097

Sift

Benign

1.0

Sift4G

Benign

1.0

Polyphen

0.0

Vest4

0.14

MutPred

0.11

Gain of phosphorylation at H279 (P = 0.0186);

MVP

0.17

MPC

0.51

ClinPred

0.013

GERP RS

1.4

Varity_R

0.022

gMVP

0.27

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