rs7977332

chr12-112427996-T-Cchr12-112427996-T-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002834.5(PTPN11):c.14+8871T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.229 in 152,044 control chromosomes in the GnomAD database, including 6,524 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.23 (6524 hom., cov: 31)
• Consequence: PTPN11 NM_002834.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.99

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.09).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.832 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PTPN11	NM_002834.5	c.14+8871T>C		intron_variant		ENST00000351677.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PTPN11	ENST00000351677.7	c.14+8871T>C		intron_variant		1	NM_002834.5	A1

Frequencies

GnomAD3 genomes AF: 0.229 AC: 34773 AN: 151926 Hom.: 6510 Cov.: 31

Gnomad AFR AF: 0.413

Gnomad AMI AF: 0.0230

Gnomad AMR AF: 0.244

Gnomad ASJ AF: 0.0369

Gnomad EAS AF: 0.854

Gnomad SAS AF: 0.245

Gnomad FIN AF: 0.114

Gnomad MID AF: 0.177

Gnomad NFE AF: 0.0965

Gnomad OTH AF: 0.203

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.229 AC: 34840 AN: 152044 Hom.: 6524 Cov.: 31 AF XY: 0.234 AC XY: 17368 AN XY: 74338

Gnomad4 AFR AF: 0.413

Gnomad4 AMR AF: 0.244

Gnomad4 ASJ AF: 0.0369

Gnomad4 EAS AF: 0.853

Gnomad4 SAS AF: 0.245

Gnomad4 FIN AF: 0.114

Gnomad4 NFE AF: 0.0966

Gnomad4 OTH AF: 0.202

Alfa AF: 0.171 Hom.: 449

Bravo AF: 0.252

Asia WGS AF: 0.485 AC: 1682 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.1
Cadd	Benign	0.091
Dann	Benign	0.30

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: rs7977332; hg19: chr12-112865800;