chr12-112484725-G-A

Position:

• chr12-112484725-G-A

Variant summary

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

The NM_002834.5(PTPN11):​c.1225-1750G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.341 in 151,682 control chromosomes in the GnomAD database, including 12,599 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 0.34 (12599 hom., cov: 31)
• Consequence: PTPN11 NM_002834.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.396

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.83 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PTPN11	NM_002834.5	c.1225-1750G>A		intron_variant		ENST00000351677.7	NP_002825.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PTPN11	ENST00000351677.7	c.1225-1750G>A		intron_variant		1	NM_002834.5	ENSP00000340944.3
PTPN11	ENST00000635625.1	c.1225-1738G>A		intron_variant		5		ENSP00000489597.1
PTPN11	ENST00000635652.1	c.217-1729G>A		intron_variant		3		ENSP00000489541.1

Frequencies

GnomAD3 genomes AF: 0.341 AC: 51647 AN: 151564 Hom.: 12575 Cov.: 31

Gnomad AFR AF: 0.633

Gnomad AMI AF: 0.145

Gnomad AMR AF: 0.332

Gnomad ASJ AF: 0.0957

Gnomad EAS AF: 0.851

Gnomad SAS AF: 0.286

Gnomad FIN AF: 0.156

Gnomad MID AF: 0.351

Gnomad NFE AF: 0.175

Gnomad OTH AF: 0.321

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

GnomAD4 genome AF: 0.341 AC: 51725 AN: 151682 Hom.: 12599 Cov.: 31 AF XY: 0.341 AC XY: 25263 AN XY: 74128

Gnomad4 AFR AF: 0.634

Gnomad4 AMR AF: 0.332

Gnomad4 ASJ AF: 0.0957

Gnomad4 EAS AF: 0.851

Gnomad4 SAS AF: 0.287

Gnomad4 FIN AF: 0.156

Gnomad4 NFE AF: 0.175

Gnomad4 OTH AF: 0.317

Alfa AF: 0.240 Hom.: 3071

Bravo AF: 0.375

Asia WGS AF: 0.514 AC: 1787 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.57
DANN	Benign	0.53

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: rs11066322; hg19: chr12-112922529;