12-6956576-G-GC

Position:

• chr12-6956576-G-GC

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BS1 BS2

The NM_002831.6(PTPN6):​c.1074+15dup variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00217 in 1,613,072 control chromosomes in the GnomAD database, including 63 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.011 (35 hom., cov: 32)
  • Exomes 𝑓: 0.0013 (28 hom.)
• Consequence: PTPN6 NM_002831.6 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.690

Genes affected

PTPN6 (HGNC:9658): (protein tyrosine phosphatase non-receptor type 6) 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. N-terminal part of this PTP contains two tandem Src homolog (SH2) domains, which act as protein phospho-tyrosine binding domains, and mediate the interaction of this PTP with its substrates. This PTP is expressed primarily in hematopoietic cells, and functions as an important regulator of multiple signaling pathways in hematopoietic cells. This PTP has been shown to interact with, and dephosphorylate a wide spectrum of phospho-proteins involved in hematopoietic cell signaling. Multiple alternatively spliced variants of this gene, which encode distinct isoforms, have been reported. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant 12-6956576-G-GC is Benign according to our data. Variant chr12-6956576-G-GC is described in ClinVar as [Benign]. Clinvar id is 783655.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0106 (1617/152076) while in subpopulation AFR AF= 0.0356 (1476/41436). AF 95% confidence interval is 0.0341. There are 35 homozygotes in gnomad4. There are 757 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 1617 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PTPN6	NM_002831.6	c.1074+15dup		intron_variant		ENST00000318974.14

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PTPN6	ENST00000318974.14	c.1074+15dup		intron_variant		1	NM_002831.6	P1
PTPN6	ENST00000399448.5	c.1080+15dup		intron_variant		1
PTPN6	ENST00000456013.5	c.1074+15dup		intron_variant		1
PTPN6	ENST00000416215.6	n.1482+15dup		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.0106 AC: 1618 AN: 151958 Hom.: 35 Cov.: 32

Gnomad AFR AF: 0.0358

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00609

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000386

Gnomad SAS AF: 0.000208

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00637

Gnomad NFE AF: 0.000397

Gnomad OTH AF: 0.00767

GnomAD3 exomes AF: 0.00309 AC: 768 AN: 248212 Hom.: 18 AF XY: 0.00230 AC XY: 311 AN XY: 135004

Gnomad AFR exome AF: 0.0392

Gnomad AMR exome AF: 0.00293

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000557

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000338

Gnomad OTH exome AF: 0.00265

GnomAD4 exome AF: 0.00129 AC: 1891 AN: 1460996 Hom.: 28 Cov.: 35 AF XY: 0.00114 AC XY: 830 AN XY: 726818

Gnomad4 AFR exome AF: 0.0368

Gnomad4 AMR exome AF: 0.00315

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.000302

Gnomad4 SAS exome AF: 0.000116

Gnomad4 FIN exome AF: 0.000170

Gnomad4 NFE exome AF: 0.000267

Gnomad4 OTH exome AF: 0.00285

GnomAD4 genome AF: 0.0106 AC: 1617 AN: 152076 Hom.: 35 Cov.: 32 AF XY: 0.0102 AC XY: 757 AN XY: 74366

Gnomad4 AFR AF: 0.0356

Gnomad4 AMR AF: 0.00608

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000386

Gnomad4 SAS AF: 0.000208

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000397

Gnomad4 OTH AF: 0.00759

Bravo AF: 0.0124

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

Invitae

Dec 26, 2018

- -

Computational scores

Source: dbNSFP v4.3

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: rs201680985; hg19: chr12-7065739;