rs2271920

Variant names:

• chr8-27458600-G-A
• rs2271920
• NM_173176.3:c.*91G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 27 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
PTK2B	NM_173176.3	c.*91G>A		3_prime_UTR_variant	Exon 31 of 31	ENST00000346049.10	NP_775268.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PTK2B	ENST00000346049.10	c.*91G>A		3_prime_UTR_variant	Exon 31 of 31	1	NM_173176.3	ENSP00000332816.6

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

African (AFR) AF: 0.607 AC: 16959 AN: 27962

American (AMR) AF: 0.402 AC: 13402 AN: 33322

Ashkenazi Jewish (ASJ) AF: 0.345 AC: 7490 AN: 21722

East Asian (EAS) AF: 0.148 AC: 5142 AN: 34846

South Asian (SAS) AF: 0.476 AC: 33414 AN: 70236

European-Finnish (FIN) AF: 0.322 AC: 11714 AN: 36368

Middle Eastern (MID) AF: 0.404 AC: 1477 AN: 3660

European-Non Finnish (NFE) AF: 0.416 AC: 389662 AN: 937188

Other (OTH) AF: 0.412 AC: 21365 AN: 51896

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

African (AFR) AF: 0.603 AC: 24992 AN: 41416

American (AMR) AF: 0.409 AC: 6254 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.340 AC: 1180 AN: 3468

East Asian (EAS) AF: 0.180 AC: 922 AN: 5126

South Asian (SAS) AF: 0.450 AC: 2165 AN: 4812

European-Finnish (FIN) AF: 0.308 AC: 3251 AN: 10558

Middle Eastern (MID) AF: 0.405 AC: 119 AN: 294

European-Non Finnish (NFE) AF: 0.405 AC: 27505 AN: 67904

Other (OTH) AF: 0.421 AC: 889 AN: 2110

Alfa AF: 0.418 Hom.: 17678

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
PhyloP100		3.7
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: rs2271920; hg19: chr8-27316117; COSMIC: COSV53557624; COSMIC: COSV53557624;