chr2-119882508-C-A

Variant names:

• chr2-119882508-C-A
• rs138361206
• NM_002830.4:c.472C>A

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP6 BS1 BS2

The NM_002830.4(PTPN4):​c.472C>A​(p.Leu158Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00393 in 1,522,120 control chromosomes in the GnomAD database, including 13 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.0026 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0041 (13 hom.)
• Consequence: PTPN4 NM_002830.4 missense
• Clinical Significance: Likely benign no assertion criteria provided B:1
• Conservation: PhyloP100: 0.517
• Publications: 7 publications found

Genes affected

PTPN4 (HGNC:9656): (protein tyrosine phosphatase non-receptor type 4) 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 protein contains a C-terminal PTP domain and an N-terminal domain homologous to the band 4.1 superfamily of cytoskeletal-associated proteins. This PTP has been shown to interact with glutamate receptor delta 2 and epsilon subunits, and is thought to play a role in signalling downstream of the glutamate receptors through tyrosine dephosphorylation. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Benign. The variant received -13 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.019843102).
• BP6: Variant 2-119882508-C-A is Benign according to our data. Variant chr2-119882508-C-A is described in ClinVar as Likely_benign. ClinVar VariationId is 3043761.Status of the report is no_assertion_criteria_provided, 0 stars.
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.00256 (390/152240) while in subpopulation NFE AF = 0.00484 (329/67988). AF 95% confidence interval is 0.00441. There are 0 homozygotes in GnomAd4. There are 181 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High AC in GnomAd4 at 390 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002830.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PTPN4	NM_002830.4	MANE Select	c.472C>A	p.Leu158Ile	missense	Exon 8 of 27	NP_002821.1	P29074

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PTPN4	ENST00000263708.7	TSL:1 MANE Select	c.472C>A	p.Leu158Ile	missense	Exon 8 of 27	ENSP00000263708.2	P29074
	PTPN4	ENST00000856005.1		c.472C>A	p.Leu158Ile	missense	Exon 9 of 28	ENSP00000526064.1
	PTPN4	ENST00000856006.1		c.472C>A	p.Leu158Ile	missense	Exon 9 of 28	ENSP00000526065.1

Frequencies

GnomAD3 genomes AF: 0.00256 AC: 390 AN: 152122 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000869

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000393

Gnomad ASJ AF: 0.00231

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.000189

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00484

Gnomad OTH AF: 0.00335

GnomAD2 exomes AF: 0.00223 AC: 353 AN: 157946 AF XY: 0.00211

Gnomad AFR exome AF: 0.000531

Gnomad AMR exome AF: 0.000803

Gnomad ASJ exome AF: 0.00109

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000341

Gnomad NFE exome AF: 0.00432

Gnomad OTH exome AF: 0.00187

GnomAD4 exome AF: 0.00408 AC: 5586 AN: 1369880 Hom.: 13 Cov.: 30 AF XY: 0.00397 AC XY: 2692 AN XY: 677674

African (AFR) AF: 0.000595 AC: 18 AN: 30268

American (AMR) AF: 0.000522 AC: 15 AN: 28736

Ashkenazi Jewish (ASJ) AF: 0.00167 AC: 41 AN: 24602

East Asian (EAS) AF: 0.00 AC: 0 AN: 36794

South Asian (SAS) AF: 0.000878 AC: 65 AN: 74044

European-Finnish (FIN) AF: 0.000436 AC: 22 AN: 50444

Middle Eastern (MID) AF: 0.000178 AC: 1 AN: 5604

European-Non Finnish (NFE) AF: 0.00493 AC: 5236 AN: 1062490

Other (OTH) AF: 0.00330 AC: 188 AN: 56898

GnomAD4 genome AF: 0.00256 AC: 390 AN: 152240 Hom.: 0 Cov.: 32 AF XY: 0.00243 AC XY: 181 AN XY: 74446

African (AFR) AF: 0.000866 AC: 36 AN: 41560

American (AMR) AF: 0.000392 AC: 6 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.00231 AC: 8 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.000415 AC: 2 AN: 4822

European-Finnish (FIN) AF: 0.000189 AC: 2 AN: 10598

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00484 AC: 329 AN: 67988

Other (OTH) AF: 0.00331 AC: 7 AN: 2112

Alfa AF: 0.00394 Hom.: 3

Bravo AF: 0.00264

TwinsUK AF: 0.00539 AC: 20

ALSPAC AF: 0.00493 AC: 19

ESP6500AA AF: 0.000687 AC: 3

ESP6500EA AF: 0.00444 AC: 38

ExAC AF: 0.00171 AC: 202

Asia WGS AF: 0.000289 AC: 1 AN: 3476

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	PTPN4-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.34	T
BayesDel_noAF	Benign	-0.25
CADD	Benign	17
DANN	Uncertain	0.99
DEOGEN2	Benign	0.21	T
Eigen	Uncertain	0.27
Eigen_PC	Benign	0.22
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Uncertain	0.89	D
MetaRNN	Benign	0.020	T
MetaSVM	Uncertain	-0.24	T
MutationAssessor	Benign	1.8	L
PhyloP100		0.52
PrimateAI	Uncertain	0.57	T
PROVEAN	Benign	-1.2	N
REVEL	Uncertain	0.39
Sift	Uncertain	0.021	D
Sift4G	Uncertain	0.034	D
Polyphen		0.94	P
Vest4		0.35
MVP		0.60
MPC		1.4
ClinPred		0.025	T
GERP RS		1.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.10
gMVP		0.30
Mutation Taster		=95/5	polymorphism

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

Other links and lift over

dbSNP: rs138361206; hg19: chr2-120640084; COSMIC: COSV55304195; COSMIC: COSV55304195;