14-88472396-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_007039.4(PTPN21):c.2719C>G(p.Arg907Gly) variant causes a missense change. The variant allele was found at a frequency of 0.00000342 in 1,461,680 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000034 (0 hom.)
• Consequence: PTPN21 NM_007039.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.23

Genes affected

PTPN21 (HGNC:9651): (protein tyrosine phosphatase non-receptor type 21) 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 an N-terminal domain, similar to cytoskeletal- associated proteins including band 4.1, ezrin, merlin, and radixin. This PTP was shown to specially interact with BMX/ETK, a member of Tec tyrosine kinase family characterized by a multimodular structures including PH, SH3, and SH2 domains. The interaction of this PTP with BMX kinase was found to increase the activation of STAT3, but not STAT2 kinase. Studies of the similar gene in mice suggested the possible roles of this PTP in liver regeneration and spermatogenesis. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PTPN21	NM_007039.4	c.2719C>G	p.Arg907Gly	missense_variant	15/19	ENST00000556564.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PTPN21	ENST00000556564.6	c.2719C>G	p.Arg907Gly	missense_variant	15/19	1	NM_007039.4	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000342 AC: 5 AN: 1461680 Hom.: 0 Cov.: 31 AF XY: 0.00000275 AC XY: 2 AN XY: 727160

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000450

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

EpiCase AF: 0.0000545

EpiControl AF: 0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 25, 2023

The c.2719C>G (p.R907G) alteration is located in exon 15 (coding exon 14) of the PTPN21 gene. This alteration results from a C to G substitution at nucleotide position 2719, causing the arginine (R) at amino acid position 907 to be replaced by a glycine (G). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.47
BayesDel_addAF	Pathogenic	0.16	D
BayesDel_noAF	Uncertain	0.0
Cadd	Uncertain	25
Dann	Uncertain	1.0
DEOGEN2	Benign	0.14	T;T
Eigen	Uncertain	0.44
Eigen_PC	Uncertain	0.52
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Uncertain	0.90	D;.
M_CAP	Benign	0.019	T
MetaRNN	Uncertain	0.67	D;D
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.55	N;N
MutationTaster	Benign	0.99	D;D
PrimateAI	Uncertain	0.51	T
PROVEAN	Uncertain	-3.6	D;D
REVEL	Benign	0.24
Sift	Uncertain	0.0020	D;D
Sift4G	Uncertain	0.014	D;D
Polyphen		0.96	D;D
Vest4		0.72
MutPred		0.51		Loss of stability (P = 0.008);Loss of stability (P = 0.008);
MVP		0.55
MPC		1.1
ClinPred		0.96	D
GERP RS		4.9
Varity_R		0.42

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr14-88938740;