rs2271920

chr8-27458600-G-A

Variant summary

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

The NM_173176.3(PTK2B):c.*91G>A variant causes a 3 prime UTR change. The variant allele was found at a frequency of 0.415 in 1,369,084 control chromosomes in the GnomAD database, including 121,505 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 0.45 (16105 hom., cov: 32)
  • Exomes 𝑓: 0.41 (105400 hom.)
• Consequence: PTK2B NM_173176.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.71

Genes affected

PTK2B (HGNC:9612): (protein tyrosine kinase 2 beta) This gene encodes a cytoplasmic protein tyrosine kinase which is involved in calcium-induced regulation of ion channels and activation of the map kinase signaling pathway. The encoded protein may represent an important signaling intermediate between neuropeptide-activated receptors or neurotransmitters that increase calcium flux and the downstream signals that regulate neuronal activity. The encoded protein undergoes rapid tyrosine phosphorylation and activation in response to increases in the intracellular calcium concentration, nicotinic acetylcholine receptor activation, membrane depolarization, or protein kinase C activation. This protein has been shown to bind CRK-associated substrate, nephrocystin, GTPase regulator associated with FAK, and the SH2 domain of GRB2. The encoded protein is a member of the FAK subfamily of protein tyrosine kinases but lacks significant sequence similarity to kinases from other subfamilies. Four transcript variants encoding two different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.52).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.597 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PTK2B	NM_173176.3	c.*91G>A		3_prime_UTR_variant	31/31	ENST00000346049.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PTK2B	ENST00000346049.10	c.*91G>A		3_prime_UTR_variant	31/31	1	NM_173176.3	A1
PTK2B	ENST00000397501.5	c.*91G>A		3_prime_UTR_variant	36/36	1		A1
PTK2B	ENST00000420218.3	c.*91G>A		3_prime_UTR_variant	30/30	5		P3
PTK2B	ENST00000517339.5	c.*91G>A		3_prime_UTR_variant	29/29	2		P3

Frequencies

GnomAD3 genomes AF: 0.447 AC: 67800 AN: 151766 Hom.: 16093 Cov.: 32

Gnomad AFR AF: 0.604

Gnomad AMI AF: 0.613

Gnomad AMR AF: 0.409

Gnomad ASJ AF: 0.340

Gnomad EAS AF: 0.180

Gnomad SAS AF: 0.449

Gnomad FIN AF: 0.308

Gnomad MID AF: 0.402

Gnomad NFE AF: 0.405

Gnomad OTH AF: 0.424

GnomAD4 exome AF: 0.411 AC: 500625 AN: 1217200 Hom.: 105400 Cov.: 18 AF XY: 0.411 AC XY: 247858 AN XY: 602548

Gnomad4 AFR exome AF: 0.607

Gnomad4 AMR exome AF: 0.402

Gnomad4 ASJ exome AF: 0.345

Gnomad4 EAS exome AF: 0.148

Gnomad4 SAS exome AF: 0.476

Gnomad4 FIN exome AF: 0.322

Gnomad4 NFE exome AF: 0.416

Gnomad4 OTH exome AF: 0.412

GnomAD4 genome AF: 0.447 AC: 67834 AN: 151884 Hom.: 16105 Cov.: 32 AF XY: 0.440 AC XY: 32675 AN XY: 74208

Gnomad4 AFR AF: 0.603

Gnomad4 AMR AF: 0.409

Gnomad4 ASJ AF: 0.340

Gnomad4 EAS AF: 0.180

Gnomad4 SAS AF: 0.450

Gnomad4 FIN AF: 0.308

Gnomad4 NFE AF: 0.405

Gnomad4 OTH AF: 0.421

Alfa AF: 0.409 Hom.: 12830

Bravo AF: 0.460

Asia WGS AF: 0.349 AC: 1216 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.52
Cadd	Benign	15
Dann	Benign	0.78

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: rs2271920; hg19: chr8-27316117; COSMIC: COSV53557624; COSMIC: COSV53557624;