Variant rs7972574 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -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:4

Conservation

PhyloP100: -1.41

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 id 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/exons	MANE	UniProt
PTPN11	NM_002834.5 linkuse as main transcript	c.14+25G>C		intron_variant		ENST00000351677.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PTPN11	ENST00000351677.7 linkuse as main transcript	c.14+25G>C		intron_variant		1	NM_002834.5	A1	Q06124-2

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

GnomAD3 exomes

AF:

0.0189

AC:

1855

AN:

97960

Hom.:

AF XY:

0.0182

AC XY:

998

AN XY:

54766

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 SAS exome

AF:

0.0212

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

Gnomad4 AFR exome

AF:

0.157

Gnomad4 AMR exome

AF:

0.0202

Gnomad4 ASJ exome

AF:

0.00345

Gnomad4 EAS exome

AF:

0.00468

Gnomad4 SAS exome

AF:

0.0202

Gnomad4 FIN exome

AF:

0.0136

Gnomad4 NFE exome

AF:

0.0131

Gnomad4 OTH exome

AF:

0.0248

GnomAD4 genome

AF:

0.0524

AC:

7966

AN:

152140

Hom.:

490

Cov.:

AF XY:

0.0505

AC XY:

3755

AN XY:

74388

show subpopulations

Gnomad4 AFR

AF:

0.150

Gnomad4 AMR

AF:

0.0308

Gnomad4 ASJ

AF:

0.00317

Gnomad4 EAS

AF:

0.00834

Gnomad4 SAS

AF:

0.0174

Gnomad4 FIN

AF:

0.0108

Gnomad4 NFE

AF:

0.0135

Gnomad4 OTH

AF:

0.0455

Alfa

AF:

0.0341

Hom.:

Bravo

AF:

0.0579

Asia WGS

AF:

0.0220

AC:

AN:

3450

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Juvenile myelomonocytic leukemia

Benign:1

Benign, criteria provided, single submitter

clinical testing

KCCC/NGS Laboratory, Kuwait Cancer Control Center

Jul 07, 2023

- -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Mar 03, 2015

- -

Noonan syndrome

Benign:1

Benign, no assertion criteria provided

clinical testing

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

May 29, 2014

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

Cadd

Benign

0.71

Dann

Benign

0.75

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

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