rs2295136

Variant names:

• chr14-88468358-G-A
• rs2295136
• NM_007039.4:c.3397-93C>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.3397-93C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.382 in 1,279,722 control chromosomes in the GnomAD database, including 96,200 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 0.35 (9858 hom., cov: 32)
  • Exomes 𝑓: 0.39 (86342 hom.)
• Consequence: PTPN21 NM_007039.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.744
• Publications: 8 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]

SPATA7 (HGNC:20423): (spermatogenesis associated 7) This gene, originally isolated from testis, is also expressed in retina. Mutations in this gene are associated with Leber congenital amaurosis and juvenile retinitis pigmentosa. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, May 2010]

SPATA7 Gene-Disease associations (from GenCC):

• Leber congenital amaurosis 3

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae), Ambry Genetics
• Leber congenital amaurosis

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• retinitis pigmentosa

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• severe early-childhood-onset retinal dystrophy

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.402 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PTPN21	NM_007039.4	c.3397-93C>T		intron_variant	Intron 18 of 18	ENST00000556564.6	NP_008970.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PTPN21	ENST00000556564.6	c.3397-93C>T		intron_variant	Intron 18 of 18	1	NM_007039.4	ENSP00000452414.1

Frequencies

GnomAD3 genomes AF: 0.352 AC: 53452 AN: 151948 Hom.: 9863 Cov.: 32

Gnomad AFR AF: 0.304

Gnomad AMI AF: 0.424

Gnomad AMR AF: 0.259

Gnomad ASJ AF: 0.467

Gnomad EAS AF: 0.187

Gnomad SAS AF: 0.265

Gnomad FIN AF: 0.391

Gnomad MID AF: 0.418

Gnomad NFE AF: 0.406

Gnomad OTH AF: 0.377

GnomAD4 exome AF: 0.387 AC: 436002 AN: 1127656 Hom.: 86342 AF XY: 0.384 AC XY: 215757 AN XY: 561632

African (AFR) AF: 0.303 AC: 7447 AN: 24594

American (AMR) AF: 0.200 AC: 4855 AN: 24328

Ashkenazi Jewish (ASJ) AF: 0.476 AC: 9018 AN: 18950

East Asian (EAS) AF: 0.175 AC: 6274 AN: 35814

South Asian (SAS) AF: 0.264 AC: 16114 AN: 61046

European-Finnish (FIN) AF: 0.382 AC: 15825 AN: 41396

Middle Eastern (MID) AF: 0.440 AC: 1430 AN: 3250

European-Non Finnish (NFE) AF: 0.410 AC: 356473 AN: 869954

Other (OTH) AF: 0.384 AC: 18566 AN: 48324

GnomAD4 genome AF: 0.352 AC: 53452 AN: 152066 Hom.: 9858 Cov.: 32 AF XY: 0.346 AC XY: 25725 AN XY: 74338

African (AFR) AF: 0.304 AC: 12608 AN: 41480

American (AMR) AF: 0.258 AC: 3951 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.467 AC: 1622 AN: 3472

East Asian (EAS) AF: 0.187 AC: 967 AN: 5164

South Asian (SAS) AF: 0.265 AC: 1275 AN: 4814

European-Finnish (FIN) AF: 0.391 AC: 4136 AN: 10572

Middle Eastern (MID) AF: 0.418 AC: 122 AN: 292

European-Non Finnish (NFE) AF: 0.406 AC: 27598 AN: 67958

Other (OTH) AF: 0.373 AC: 786 AN: 2108

Alfa AF: 0.385 Hom.: 20256

Bravo AF: 0.341

Asia WGS AF: 0.213 AC: 743 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	7.3
DANN	Benign	0.53
PhyloP100		0.74
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: rs2295136; hg19: chr14-88934702; COSMIC: COSV60846311; COSMIC: COSV60846311;