NM_005157.6:c.2116G>A

Variant names:

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_005157.6(ABL1):c.2116G>A(p.Gly706Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00233 in 1,612,018 control chromosomes in the GnomAD database, including 14 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G706V) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.0019 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0024 ( 14 hom. )

Consequence

ABL1
NM_005157.6 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5O:1

Conservation

PhyloP100: 1.75

Publications

10 publications found

Variant links:

Genes affected

ABL1 (HGNC:76): (ABL proto-oncogene 1, non-receptor tyrosine kinase) This gene is a protooncogene that encodes a protein tyrosine kinase involved in a variety of cellular processes, including cell division, adhesion, differentiation, and response to stress. The activity of the protein is negatively regulated by its SH3 domain, whereby deletion of the region encoding this domain results in an oncogene. The ubiquitously expressed protein has DNA-binding activity that is regulated by CDC2-mediated phosphorylation, suggesting a cell cycle function. This gene has been found fused to a variety of translocation partner genes in various leukemias, most notably the t(9;22) translocation that results in a fusion with the 5' end of the breakpoint cluster region gene (BCR; MIM:151410). Alternative splicing of this gene results in two transcript variants, which contain alternative first exons that are spliced to the remaining common exons. [provided by RefSeq, Aug 2014]

ABL1 Gene-Disease associations (from GenCC):

congenital heart defects and skeletal malformations syndrome
Inheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae), PanelApp Australia, G2P
connective tissue disorder
Inheritance: AD Classification: MODERATE Submitted by: Genomics England PanelApp
bone development disease
Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

ABL1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.003545463).

BP6

Variant 9-130884406-G-A is Benign according to our data. Variant chr9-130884406-G-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 133445.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAdExome4 at 14 AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ABL1	NM_005157.6 link	c.2116G>A	p.Gly706Ser	missense_variant	Exon 11 of 11	ENST00000318560.6	NP_005148.2	P00519-1A0A024R8E2Q59FK4
ABL1	NM_007313.3 link	c.2173G>A	p.Gly725Ser	missense_variant	Exon 11 of 11		NP_009297.2	P00519-2Q59FK4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ABL1	ENST00000318560.6 link	c.2116G>A	p.Gly706Ser	missense_variant	Exon 11 of 11	1	NM_005157.6	ENSP00000323315.5		P00519-1
ABL1	ENST00000372348.9 link	c.2173G>A	p.Gly725Ser	missense_variant	Exon 11 of 11	1		ENSP00000361423.2		P00519-2

Frequencies

GnomAD3 genomes

AF:

0.00192

AC:

293

AN:

152222

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000796

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00196

Gnomad ASJ

AF:

0.00835

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00600

Gnomad FIN

AF:

0.00122

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00225

Gnomad OTH

AF:

0.00287

GnomAD2 exomes

AF:

0.00254

AC:

623

AN:

245420

AF XY:

0.00281

show subpopulations

Gnomad AFR exome

AF:

0.000651

Gnomad AMR exome

AF:

0.00230

Gnomad ASJ exome

AF:

0.00887

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00181

Gnomad NFE exome

AF:

0.00220

Gnomad OTH exome

AF:

0.00299

GnomAD4 exome

AF:

0.00237

AC:

3462

AN:

1459678

Hom.:

Cov.:

AF XY:

0.00249

AC XY:

1809

AN XY:

726158

show subpopulations

African (AFR)

AF:

0.000986

AC:

AN:

33476

American (AMR)

AF:

0.00249

AC:

111

AN:

44666

Ashkenazi Jewish (ASJ)

AF:

0.00927

AC:

242

AN:

26108

East Asian (EAS)

AF:

0.0000252

AC:

AN:

39690

South Asian (SAS)

AF:

0.00415

AC:

358

AN:

86234

European-Finnish (FIN)

AF:

0.00159

AC:

AN:

51604

Middle Eastern (MID)

AF:

0.00521

AC:

AN:

5762

European-Non Finnish (NFE)

AF:

0.00218

AC:

2420

AN:

1111784

Other (OTH)

AF:

0.00307

AC:

185

AN:

60354

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.494

Heterozygous variant carriers

237

474

711

948

1185

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

180

270

360

450

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00193

AC:

294

AN:

152340

Hom.:

Cov.:

AF XY:

0.00216

AC XY:

161

AN XY:

74500

show subpopulations

African (AFR)

AF:

0.000794

AC:

AN:

41584

American (AMR)

AF:

0.00196

AC:

AN:

15308

Ashkenazi Jewish (ASJ)

AF:

0.00835

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5166

South Asian (SAS)

AF:

0.00600

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00122

AC:

AN:

10628

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00226

AC:

154

AN:

68032

Other (OTH)

AF:

0.00284

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00256

Hom.:

Bravo

AF:

0.00181

TwinsUK

AF:

0.00189

AC:

ALSPAC

AF:

0.00104

AC:

ESP6500AA

AF:

0.000910

AC:

ESP6500EA

AF:

0.00210

AC:

ExAC

AF:

0.00234

AC:

284

Asia WGS

AF:

0.00144

AC:

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:5Other:1

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:4

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center

Significance:Likely benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Feb 01, 2025

CeGaT Center for Human Genetics Tuebingen

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

ABL1: PM5, BP4, BS2 -

Jan 30, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not specified

Benign:1Other:1

Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Sep 19, 2013

ITMI

Significance:not provided

Review Status:no classification provided

Collection Method:reference population

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.062

BayesDel_addAF

Benign

-0.66

BayesDel_noAF

Benign

-0.71

CADD

Benign

2.8

(source)

DANN

Benign

0.65

DEOGEN2

Benign

0.18

.;T

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.17

LIST_S2

Benign

0.75

T;T

M_CAP

Benign

0.0027

MetaRNN

Benign

0.0035

T;T

MetaSVM

Benign

-0.95

MutationAssessor

Benign

-0.46

.;N

PhyloP100

1.8

PrimateAI

Benign

0.31

PROVEAN

Benign

0.29

N;N

REVEL

Benign

0.024

Sift

Benign

1.0

T;T

Sift4G

Benign

0.83

T;T

Polyphen

0.0010

.;B

Vest4

0.089

MVP

0.23

MPC

0.21

ClinPred

0.00061

GERP RS

0.96

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.8

Varity_R

0.016

gMVP

0.076

Mutation Taster

=99/1

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over