Variant 1-179108917-T-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_007314.4(ABL2):c.2350A>T(p.Thr784Ser) variant causes a missense change. The variant allele was found at a frequency of 0.0034 in 1,614,082 control chromosomes in the GnomAD database, including 24 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0029 ( 2 hom., cov: 32)

Exomes 𝑓: 0.0034 ( 22 hom. )

Consequence

ABL2
NM_007314.4 missense

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 5.73

Variant links:

Genes affected

ABL2 (HGNC:77): (ABL proto-oncogene 2, non-receptor tyrosine kinase) This gene encodes a member of the Abelson family of nonreceptor tyrosine protein kinases. The protein is highly similar to the c-abl oncogene 1 protein, including the tyrosine kinase, SH2 and SH3 domains, and it plays a role in cytoskeletal rearrangements through its C-terminal F-actin- and microtubule-binding sequences. This gene is expressed in both normal and tumor cells, and is involved in translocation with the ets variant 6 gene in leukemia. Multiple alternatively spliced transcript variants encoding different protein isoforms have been found for this gene. [provided by RefSeq, Nov 2009]

ABL2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.008987635).

BP6

Variant 1-179108917-T-A is Benign according to our data. Variant chr1-179108917-T-A is described in ClinVar as [Likely_benign]. Clinvar id is 715839.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High AC in GnomAd4 at 446 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ABL2	NM_007314.4 linkuse as main transcript	c.2350A>T	p.Thr784Ser	missense_variant	12/12	ENST00000502732.6	NP_009298.1	P42684-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ABL2	ENST00000502732.6 linkuse as main transcript	c.2350A>T	p.Thr784Ser	missense_variant	12/12	1	NM_007314.4	ENSP00000427562.1		P42684-1

Frequencies

GnomAD3 genomes

AF:

0.00293

AC:

445

AN:

152072

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000700

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00367

Gnomad ASJ

AF:

0.0130

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00166

Gnomad FIN

AF:

0.00424

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00372

Gnomad OTH

AF:

0.00382

GnomAD3 exomes

AF:

0.00328

AC:

825

AN:

251444

Hom.:

AF XY:

0.00338

AC XY:

459

AN XY:

135904

show subpopulations

Gnomad AFR exome

AF:

0.000492

Gnomad AMR exome

AF:

0.00162

Gnomad ASJ exome

AF:

0.0134

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.00186

Gnomad FIN exome

AF:

0.00439

Gnomad NFE exome

AF:

0.00399

Gnomad OTH exome

AF:

0.00310

GnomAD4 exome

AF:

0.00345

AC:

5041

AN:

1461892

Hom.:

Cov.:

AF XY:

0.00344

AC XY:

2501

AN XY:

727248

show subpopulations

Gnomad4 AFR exome

AF:

0.000538

Gnomad4 AMR exome

AF:

0.00154

Gnomad4 ASJ exome

AF:

0.0138

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00159

Gnomad4 FIN exome

AF:

0.00502

Gnomad4 NFE exome

AF:

0.00355

Gnomad4 OTH exome

AF:

0.00325

GnomAD4 genome

AF:

0.00293

AC:

446

AN:

152190

Hom.:

Cov.:

AF XY:

0.00316

AC XY:

235

AN XY:

74420

show subpopulations

Gnomad4 AFR

AF:

0.000698

Gnomad4 AMR

AF:

0.00367

Gnomad4 ASJ

AF:

0.0130

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00187

Gnomad4 FIN

AF:

0.00424

Gnomad4 NFE

AF:

0.00372

Gnomad4 OTH

AF:

0.00378

Alfa

AF:

0.00395

Hom.:

Bravo

AF:

0.00247

TwinsUK

AF:

0.00431

AC:

ALSPAC

AF:

0.00337

AC:

ESP6500AA

AF:

0.000454

AC:

ESP6500EA

AF:

0.00512

AC:

ExAC

AF:

0.00314

AC:

381

EpiCase

AF:

0.00409

EpiControl

AF:

0.00409

ClinVar

Significance: Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Dec 01, 2022	ABL2: BS2 -
Likely benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jul 04, 2018	- -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.42

BayesDel_addAF

Benign

-0.45

BayesDel_noAF

Benign

-0.42

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.057

T;.;.

Eigen

Uncertain

0.49

Eigen_PC

Uncertain

0.57

FATHMM_MKL

Uncertain

0.97

LIST_S2

Uncertain

0.87

D;D;D

M_CAP

Benign

0.010

MetaRNN

Benign

0.0090

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.55

N;.;.

PrimateAI

Uncertain

0.72

PROVEAN

Benign

-0.28

N;N;N

REVEL

Benign

0.14

Sift

Benign

0.20

T;T;T

Sift4G

Benign

0.79

T;T;T

Polyphen

0.89

P;D;D

Vest4

0.50

MVP

0.79

MPC

0.59

ClinPred

0.019

GERP RS

5.8

Varity_R

0.10

gMVP

0.16

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

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