rs4767860

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_002834.5(PTPN11):c.1713-146G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0619 in 664,276 control chromosomes in the GnomAD database, including 8,595 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.056 ( 1313 hom., cov: 33)

Exomes 𝑓: 0.063 ( 7282 hom. )

Consequence

PTPN11
NM_002834.5 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.698

Publications

9 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 -14 ACMG points.

BP4

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

BP6

Variant 12-112504549-G-A is Benign according to our data. Variant chr12-112504549-G-A is described in ClinVar as Benign. ClinVar VariationId is 1293594.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.597 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
PTPN11	NM_002834.5 link	c.1713-146G>A	intron_variant	Intron 14 of 15	ENST00000351677.7	NP_002825.3	Q06124-2
PTPN11	NM_001330437.2 link	c.1725-146G>A	intron_variant	Intron 14 of 15		NP_001317366.1	Q06124-1
PTPN11	NM_001374625.1 link	c.1710-146G>A	intron_variant	Intron 14 of 15		NP_001361554.1
PTPN11	XM_011538613.3 link	c.1722-146G>A	intron_variant	Intron 14 of 15		XP_011536915.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PTPN11	ENST00000351677.7 link	c.1713-146G>A		intron_variant	Intron 14 of 15	1	NM_002834.5	ENSP00000340944.3		Q06124-2
PTPN11	ENST00000635625.1 link	c.1725-146G>A		intron_variant	Intron 14 of 14	5		ENSP00000489597.1		Q06124-1

Frequencies

GnomAD3 genomes

AF:

0.0565

AC:

8593

AN:

152132

Hom.:

1318

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0564

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.144

Gnomad ASJ

AF:

0.00547

Gnomad EAS

AF:

0.615

Gnomad SAS

AF:

0.0964

Gnomad FIN

AF:

0.00217

Gnomad MID

AF:

0.0475

Gnomad NFE

AF:

0.00322

Gnomad OTH

AF:

0.0641

GnomAD4 exome

AF:

0.0634

AC:

32488

AN:

512026

Hom.:

7282

AF XY:

0.0620

AC XY:

17033

AN XY:

274666

show subpopulations

African (AFR)

AF:

0.0527

AC:

716

AN:

13582

American (AMR)

AF:

0.195

AC:

5137

AN:

26386

Ashkenazi Jewish (ASJ)

AF:

0.00499

AC:

AN:

16822

East Asian (EAS)

AF:

0.643

AC:

19585

AN:

30456

South Asian (SAS)

AF:

0.0784

AC:

4230

AN:

53980

European-Finnish (FIN)

AF:

0.00335

AC:

148

AN:

44178

Middle Eastern (MID)

AF:

0.0300

AC:

AN:

2164

European-Non Finnish (NFE)

AF:

0.00343

AC:

1019

AN:

296788

Other (OTH)

AF:

0.0544

AC:

1504

AN:

27670

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.509

Heterozygous variant carriers

862

1724

2587

3449

4311

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

246

492

738

984

1230

<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:

0.0565

AC:

8598

AN:

152250

Hom.:

1313

Cov.:

AF XY:

0.0630

AC XY:

4688

AN XY:

74438

show subpopulations

African (AFR)

AF:

0.0563

AC:

2340

AN:

41550

American (AMR)

AF:

0.144

AC:

2201

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.00547

AC:

AN:

3472

East Asian (EAS)

AF:

0.615

AC:

3179

AN:

5172

South Asian (SAS)

AF:

0.0971

AC:

468

AN:

4818

European-Finnish (FIN)

AF:

0.00217

AC:

AN:

10622

Middle Eastern (MID)

AF:

0.0510

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00322

AC:

219

AN:

68016

Other (OTH)

AF:

0.0634

AC:

134

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

302

604

906

1208

1510

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

176

264

352

440

<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:

0.0156

Hom.:

184

Bravo

AF:

0.0718

Asia WGS

AF:

0.245

AC:

848

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Mar 03, 2015

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

0.66

(source)

DANN

Benign

0.56

PhyloP100

-0.70

Mutation Taster

=99/1

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