rs2274736

Variant names:

• chr14-88472308-A-G
• rs2274736
• NM_007039.4:c.2807T>C

Your query was ambiguous. Multiple possible variants found:

• chr14-88472308-A-G
• chr14-88472308-A-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_007039.4(PTPN21):​c.2807T>C​(p.Val936Ala) variant causes a missense change. The variant allele was found at a frequency of 0.342 in 1,612,314 control chromosomes in the GnomAD database, including 96,549 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.37 (11193 hom., cov: 31)
  • Exomes 𝑓: 0.34 (85356 hom.)
• Consequence: PTPN21 NM_007039.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.05
• Publications: 41 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0070250034).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.491 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_007039.4. 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
	PTPN21	NM_007039.4	MANE Select	c.2807T>C	p.Val936Ala	missense	Exon 15 of 19	NP_008970.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PTPN21	ENST00000556564.6	TSL:1 MANE Select	c.2807T>C	p.Val936Ala	missense	Exon 15 of 19	ENSP00000452414.1
	PTPN21	ENST00000328736.7	TSL:1	c.2807T>C	p.Val936Ala	missense	Exon 14 of 18	ENSP00000330276.3
	PTPN21	ENST00000536337.5	TSL:1	n.*2744T>C		non_coding_transcript_exon	Exon 15 of 19	ENSP00000443951.1

Frequencies

GnomAD3 genomes AF: 0.374 AC: 56725 AN: 151724 Hom.: 11168 Cov.: 31

Gnomad AFR AF: 0.496

Gnomad AMI AF: 0.373

Gnomad AMR AF: 0.271

Gnomad ASJ AF: 0.329

Gnomad EAS AF: 0.343

Gnomad SAS AF: 0.421

Gnomad FIN AF: 0.284

Gnomad MID AF: 0.269

Gnomad NFE AF: 0.340

Gnomad OTH AF: 0.333

GnomAD2 exomes AF: 0.334 AC: 83909 AN: 251380 AF XY: 0.334

Gnomad AFR exome AF: 0.507

Gnomad AMR exome AF: 0.229

Gnomad ASJ exome AF: 0.333

Gnomad EAS exome AF: 0.332

Gnomad FIN exome AF: 0.279

Gnomad NFE exome AF: 0.336

Gnomad OTH exome AF: 0.311

GnomAD4 exome AF: 0.338 AC: 493855 AN: 1460472 Hom.: 85356 Cov.: 33 AF XY: 0.339 AC XY: 246630 AN XY: 726650

African (AFR) AF: 0.508 AC: 17002 AN: 33456

American (AMR) AF: 0.239 AC: 10670 AN: 44714

Ashkenazi Jewish (ASJ) AF: 0.333 AC: 8709 AN: 26126

East Asian (EAS) AF: 0.326 AC: 12932 AN: 39682

South Asian (SAS) AF: 0.390 AC: 33619 AN: 86230

European-Finnish (FIN) AF: 0.283 AC: 15127 AN: 53408

Middle Eastern (MID) AF: 0.259 AC: 1493 AN: 5764

European-Non Finnish (NFE) AF: 0.336 AC: 373553 AN: 1110750

Other (OTH) AF: 0.344 AC: 20750 AN: 60342

GnomAD4 genome AF: 0.374 AC: 56822 AN: 151842 Hom.: 11193 Cov.: 31 AF XY: 0.368 AC XY: 27341 AN XY: 74200

African (AFR) AF: 0.496 AC: 20543 AN: 41378

American (AMR) AF: 0.272 AC: 4144 AN: 15252

Ashkenazi Jewish (ASJ) AF: 0.329 AC: 1141 AN: 3472

East Asian (EAS) AF: 0.344 AC: 1769 AN: 5140

South Asian (SAS) AF: 0.422 AC: 2022 AN: 4794

European-Finnish (FIN) AF: 0.284 AC: 2987 AN: 10532

Middle Eastern (MID) AF: 0.272 AC: 80 AN: 294

European-Non Finnish (NFE) AF: 0.340 AC: 23086 AN: 67958

Other (OTH) AF: 0.337 AC: 711 AN: 2112

Alfa AF: 0.349 Hom.: 35198

Bravo AF: 0.376

TwinsUK AF: 0.328 AC: 1216

ALSPAC AF: 0.336 AC: 1296

ESP6500AA AF: 0.506 AC: 2230

ESP6500EA AF: 0.341 AC: 2933

ExAC AF: 0.343 AC: 41644

Asia WGS AF: 0.390 AC: 1358 AN: 3478

EpiCase AF: 0.327

EpiControl AF: 0.323

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.044
BayesDel_addAF	Benign	-0.75	T
BayesDel_noAF	Benign	-0.71
CADD	Benign	18
DANN	Benign	0.82
DEOGEN2	Benign	0.089	T
Eigen	Benign	-0.72
Eigen_PC	Benign	-0.52
FATHMM_MKL	Benign	0.38	N
LIST_S2	Benign	0.49	T
MetaRNN	Benign	0.0070	T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	-0.99	N
PhyloP100		4.0
PrimateAI	Uncertain	0.48	T
PROVEAN	Benign	1.1	N
REVEL	Benign	0.12
Sift	Benign	0.37	T
Sift4G	Benign	0.29	T
Polyphen		0.0	B
Vest4		0.048
MPC		0.37
ClinPred		0.0086	T
GERP RS		5.9
Varity_R		0.025
Mutation Taster		=100/0	polymorphism (auto)

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: rs2274736; hg19: chr14-88938652; COSMIC: COSV60848431; COSMIC: COSV60848431;