Genetic Variant PTPN21:c.350+1866A>G (chr14-88515226-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_007039.4(PTPN21):c.350+1866A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.156 in 152,198 control chromosomes in the GnomAD database, including 2,456 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 0.16 ( 2456 hom., cov: 32)

Exomes 𝑓: 0.38 ( 0 hom. )

Consequence

PTPN21
NM_007039.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.395

Publications

5 publications found

Variant links:

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]

PTPN21 links:

ENSG00000258983 (HGNC:):

ENSG00000258983 links:

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ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.6).

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.282 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.350+1866A>G		intron	N/A	NP_008970.2	Q16825

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
PTPN21	ENST00000556564.6	TSL:1 MANE Select	c.350+1866A>G	intron	N/A	ENSP00000452414.1	Q16825
PTPN21	ENST00000328736.7	TSL:1	c.350+1866A>G	intron	N/A	ENSP00000330276.3	Q16825
PTPN21	ENST00000536337.5	TSL:1	n.*287+1866A>G	intron	N/A	ENSP00000443951.1	G3V1Q9

Frequencies

GnomAD3 genomes

AF:

0.157

AC:

23809

AN:

152072

Hom.:

2453

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0410

Gnomad AMI

AF:

0.279

Gnomad AMR

AF:

0.289

Gnomad ASJ

AF:

0.215

Gnomad EAS

AF:

0.275

Gnomad SAS

AF:

0.143

Gnomad FIN

AF:

0.159

Gnomad MID

AF:

0.222

Gnomad NFE

AF:

0.183

Gnomad OTH

AF:

0.182

GnomAD4 exome

AF:

0.375

AC:

AN:

Hom.:

Cov.:

AF XY:

0.250

AC XY:

AN XY:

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.500

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.500

AC:

AN:

Other (OTH)

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.658

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.156

AC:

23813

AN:

152190

Hom.:

2456

Cov.:

AF XY:

0.158

AC XY:

11749

AN XY:

74416

show subpopulations

African (AFR)

AF:

0.0408

AC:

1697

AN:

41556

American (AMR)

AF:

0.289

AC:

4417

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.215

AC:

747

AN:

3472

East Asian (EAS)

AF:

0.275

AC:

1421

AN:

5174

South Asian (SAS)

AF:

0.143

AC:

691

AN:

4824

European-Finnish (FIN)

AF:

0.159

AC:

1682

AN:

10584

Middle Eastern (MID)

AF:

0.221

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.183

AC:

12451

AN:

67988

Other (OTH)

AF:

0.184

AC:

388

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

982

1965

2947

3930

4912

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

252

504

756

1008

1260

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.182

Hom.:

4918

Bravo

AF:

0.168

Asia WGS

AF:

0.238

AC:

831

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.60

CADD

Benign

3.5

(source)

DANN

Benign

0.73

PhyloP100

0.40

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over