rs7972574

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_002834.5(PTPN11):c.14+25G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0204 in 1,501,108 control chromosomes in the GnomAD database, including 995 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.052 ( 490 hom., cov: 33)

Exomes 𝑓: 0.017 ( 505 hom. )

Consequence

PTPN11
NM_002834.5 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: -1.41

Publications

3 publications found

Variant links:

Genes affected

PTPN11 (HGNC:9644): (protein tyrosine phosphatase non-receptor type 11) The protein encoded by this gene is a member of the protein tyrosine phosphatase (PTP) family. PTPs are known to be signaling molecules that regulate a variety of cellular processes including cell growth, differentiation, mitotic cycle, and oncogenic transformation. This PTP contains two tandem Src homology-2 domains, which function as phospho-tyrosine binding domains and mediate the interaction of this PTP with its substrates. This PTP is widely expressed in most tissues and plays a regulatory role in various cell signaling events that are important for a diversity of cell functions, such as mitogenic activation, metabolic control, transcription regulation, and cell migration. Mutations in this gene are a cause of Noonan syndrome as well as acute myeloid leukemia. [provided by RefSeq, Aug 2016]

PTPN11 Gene-Disease associations (from GenCC):

LEOPARD syndrome 1
Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P, PanelApp Australia, Genomics England PanelApp
Noonan syndrome
Inheritance: AD Classification: DEFINITIVE, SUPPORTIVE Submitted by: ClinGen, Orphanet
Noonan syndrome 1
Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Ambry Genetics, G2P, Labcorp Genetics (formerly Invitae), Genomics England PanelApp, PanelApp Australia
Noonan syndrome with multiple lentigines
Inheritance: AD Classification: DEFINITIVE, SUPPORTIVE Submitted by: ClinGen, Orphanet
metachondromatosis
Inheritance: AD Classification: STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet, Ambry Genetics
cardiofaciocutaneous syndrome
Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen
Costello syndrome
Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen

PTPN11 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.87).

BP6

Variant 12-112419150-G-C is Benign according to our data. Variant chr12-112419150-G-C is described in ClinVar as Benign. ClinVar VariationId is 40478.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.147 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PTPN11	NM_002834.5 link	c.14+25G>C		intron_variant	Intron 1 of 15	ENST00000351677.7	NP_002825.3	Q06124-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PTPN11	ENST00000351677.7 link	c.14+25G>C		intron_variant	Intron 1 of 15	1	NM_002834.5	ENSP00000340944.3		Q06124-2
PTPN11	ENST00000635625.1 link	c.14+25G>C		intron_variant	Intron 1 of 14	5		ENSP00000489597.1		Q06124-1

Frequencies

GnomAD3 genomes

AF:

0.0522

AC:

7941

AN:

152032

Hom.:

487

Cov.:

show subpopulations

Gnomad AFR

AF:

0.149

Gnomad AMI

AF:

0.00440

Gnomad AMR

AF:

0.0309

Gnomad ASJ

AF:

0.00317

Gnomad EAS

AF:

0.00831

Gnomad SAS

AF:

0.0180

Gnomad FIN

AF:

0.0108

Gnomad MID

AF:

0.0191

Gnomad NFE

AF:

0.0135

Gnomad OTH

AF:

0.0445

GnomAD2 exomes

AF:

0.0189

AC:

1855

AN:

97960

AF XY:

0.0182

show subpopulations

Gnomad AFR exome

AF:

0.185

Gnomad AMR exome

AF:

0.0189

Gnomad ASJ exome

AF:

0.00352

Gnomad EAS exome

AF:

0.0119

Gnomad FIN exome

AF:

0.0157

Gnomad NFE exome

AF:

0.0140

Gnomad OTH exome

AF:

0.0220

GnomAD4 exome

AF:

0.0168

AC:

22652

AN:

1348968

Hom.:

505

Cov.:

AF XY:

0.0164

AC XY:

10892

AN XY:

664836

show subpopulations

African (AFR)

AF:

0.157

AC:

4298

AN:

27334

American (AMR)

AF:

0.0202

AC:

644

AN:

31904

Ashkenazi Jewish (ASJ)

AF:

0.00345

AC:

AN:

23776

East Asian (EAS)

AF:

0.00468

AC:

145

AN:

31008

South Asian (SAS)

AF:

0.0202

AC:

1526

AN:

75426

European-Finnish (FIN)

AF:

0.0136

AC:

529

AN:

39018

Middle Eastern (MID)

AF:

0.0304

AC:

120

AN:

3948

European-Non Finnish (NFE)

AF:

0.0131

AC:

13921

AN:

1060652

Other (OTH)

AF:

0.0248

AC:

1387

AN:

55902

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.493

Heterozygous variant carriers

1071

2142

3214

4285

5356

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

608

1216

1824

2432

3040

<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:

0.0524

AC:

7966

AN:

152140

Hom.:

490

Cov.:

AF XY:

0.0505

AC XY:

3755

AN XY:

74388

show subpopulations

African (AFR)

AF:

0.150

AC:

6216

AN:

41518

American (AMR)

AF:

0.0308

AC:

471

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.00317

AC:

AN:

3470

East Asian (EAS)

AF:

0.00834

AC:

AN:

5156

South Asian (SAS)

AF:

0.0174

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.0108

AC:

115

AN:

10602

Middle Eastern (MID)

AF:

0.0205

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.0135

AC:

920

AN:

67966

Other (OTH)

AF:

0.0455

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

369

738

1107

1476

1845

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

168

252

336

420

<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:

0.0341

Hom.:

Bravo

AF:

0.0579

Asia WGS

AF:

0.0220

AC:

AN:

3450

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Mar 03, 2015

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

not specified

Benign:1

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Metachondromatosis

Benign:1

Feb 01, 2025

KCCC/NGS Laboratory, Kuwait Cancer Control Center

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Juvenile myelomonocytic leukemia

Benign:1

Jul 07, 2023

KCCC/NGS Laboratory, Kuwait Cancer Control Center

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Noonan syndrome

Benign:1

May 29, 2014

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

0.71

(source)

DANN

Benign

0.75

PhyloP100

-1.4

PromoterAI

0.026

Neutral

(source)

Mutation Taster

=100/0

polymorphism (auto)

(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