14-88515226-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.395

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PTPN21	NM_007039.4	c.350+1866A>G		intron_variant		ENST00000556564.6
LOC105370614	XR_007064296.1	n.479T>C		non_coding_transcript_exon_variant	3/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PTPN21	ENST00000556564.6	c.350+1866A>G		intron_variant		1	NM_007039.4	P1
	ENST00000555444.2	n.629T>C		non_coding_transcript_exon_variant	5/5	3

Frequencies

GnomAD3 genomes AF: 0.157 AC: 23809 AN: 152072 Hom.: 2453 Cov.: 32

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: 3 AN: 8 Hom.: 0 Cov.: 0 AF XY: 0.250 AC XY: 1 AN XY: 4

Gnomad4 AFR exome AF: 0.00

Gnomad4 FIN exome AF: 0.500

Gnomad4 NFE exome AF: 0.500

GnomAD4 genome AF: 0.156 AC: 23813 AN: 152190 Hom.: 2456 Cov.: 32 AF XY: 0.158 AC XY: 11749 AN XY: 74416

Gnomad4 AFR AF: 0.0408

Gnomad4 AMR AF: 0.289

Gnomad4 ASJ AF: 0.215

Gnomad4 EAS AF: 0.275

Gnomad4 SAS AF: 0.143

Gnomad4 FIN AF: 0.159

Gnomad4 NFE AF: 0.183

Gnomad4 OTH AF: 0.184

Alfa AF: 0.182 Hom.: 3943

Bravo AF: 0.168

Asia WGS AF: 0.238 AC: 831 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.60
Cadd	Benign	3.5
Dann	Benign	0.73

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

LitVar

Other links and lift over

dbSNP: rs11622270; hg19: chr14-88981570;