rs41279092

chr12-112486902-G-Achr12-112486902-G-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The ENST00000392597.5(PTPN11):c.*269G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0479 in 1,393,526 control chromosomes in the GnomAD database, including 1,945 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.039 (180 hom., cov: 32)
  • Exomes 𝑓: 0.049 (1765 hom.)
• Consequence: PTPN11 ENST00000392597.5 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0380

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP6: Variant 12-112486902-G-A is Benign according to our data. Variant chr12-112486902-G-A is described in ClinVar as [Benign]. Clinvar id is 561856.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.072 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PTPN11	NM_002834.5	c.1379+273G>A		intron_variant		ENST00000351677.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PTPN11	ENST00000351677.7	c.1379+273G>A		intron_variant		1	NM_002834.5	A1

Frequencies

GnomAD3 genomes AF: 0.0393 AC: 5986 AN: 152150 Hom.: 180 Cov.: 32

Gnomad AFR AF: 0.00714

Gnomad AMI AF: 0.154

Gnomad AMR AF: 0.0306

Gnomad ASJ AF: 0.0285

Gnomad EAS AF: 0.000578

Gnomad SAS AF: 0.0791

Gnomad FIN AF: 0.101

Gnomad MID AF: 0.0475

Gnomad NFE AF: 0.0506

Gnomad OTH AF: 0.0330

GnomAD4 exome AF: 0.0490 AC: 60810 AN: 1241258 Hom.: 1765 Cov.: 30 AF XY: 0.0498 AC XY: 29816 AN XY: 598224

Gnomad4 AFR exome AF: 0.00624

Gnomad4 AMR exome AF: 0.0233

Gnomad4 ASJ exome AF: 0.0324

Gnomad4 EAS exome AF: 0.000252

Gnomad4 SAS exome AF: 0.0778

Gnomad4 FIN exome AF: 0.0938

Gnomad4 NFE exome AF: 0.0498

Gnomad4 OTH exome AF: 0.0460

GnomAD4 genome AF: 0.0393 AC: 5982 AN: 152268 Hom.: 180 Cov.: 32 AF XY: 0.0422 AC XY: 3139 AN XY: 74436

Gnomad4 AFR AF: 0.00712

Gnomad4 AMR AF: 0.0306

Gnomad4 ASJ AF: 0.0285

Gnomad4 EAS AF: 0.000579

Gnomad4 SAS AF: 0.0785

Gnomad4 FIN AF: 0.101

Gnomad4 NFE AF: 0.0507

Gnomad4 OTH AF: 0.0326

Alfa AF: 0.0349 Hom.: 23

Bravo AF: 0.0309

Asia WGS AF: 0.0250 AC: 86 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 19, 2018

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
Cadd	Benign	3.5
Dann	Benign	0.67

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

Other links and lift over

dbSNP: rs41279092; hg19: chr12-112924706;