rs9773817

Variant names:

• chr8-27441760-A-G
• rs9773817
• NM_173176.3:c.2040-1115A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_173176.3(PTK2B):​c.2040-1115A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.146 in 152,232 control chromosomes in the GnomAD database, including 1,704 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 0.15 (1704 hom., cov: 32)
• Consequence: PTK2B NM_173176.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.485
• Publications: 9 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=-0.7).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.175 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PTK2B	NM_173176.3	c.2040-1115A>G		intron_variant	Intron 21 of 30	ENST00000346049.10	NP_775268.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PTK2B	ENST00000346049.10	c.2040-1115A>G		intron_variant	Intron 21 of 30	1	NM_173176.3	ENSP00000332816.6

Frequencies

GnomAD3 genomes AF: 0.146 AC: 22261 AN: 152116 Hom.: 1703 Cov.: 32

Gnomad AFR AF: 0.179

Gnomad AMI AF: 0.148

Gnomad AMR AF: 0.103

Gnomad ASJ AF: 0.232

Gnomad EAS AF: 0.0575

Gnomad SAS AF: 0.0677

Gnomad FIN AF: 0.130

Gnomad MID AF: 0.177

Gnomad NFE AF: 0.146

Gnomad OTH AF: 0.162

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.146 AC: 22273 AN: 152232 Hom.: 1704 Cov.: 32 AF XY: 0.142 AC XY: 10603 AN XY: 74448

African (AFR) AF: 0.179 AC: 7420 AN: 41524

American (AMR) AF: 0.103 AC: 1573 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.232 AC: 805 AN: 3468

East Asian (EAS) AF: 0.0577 AC: 299 AN: 5184

South Asian (SAS) AF: 0.0670 AC: 323 AN: 4824

European-Finnish (FIN) AF: 0.130 AC: 1378 AN: 10598

Middle Eastern (MID) AF: 0.170 AC: 50 AN: 294

European-Non Finnish (NFE) AF: 0.146 AC: 9948 AN: 68016

Other (OTH) AF: 0.162 AC: 342 AN: 2110

Alfa AF: 0.144 Hom.: 4972

Bravo AF: 0.149

Asia WGS AF: 0.0670 AC: 233 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.70
CADD	Benign	7.6
DANN	Benign	0.81
PhyloP100		0.48
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: rs9773817; hg19: chr8-27299277;