rs11994882

Positions:

• chr8-27404298-A-G
• chr8-27404298-A-T

Variant summary

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

The NM_173176.3(PTK2B):​c.204+6510A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.841 in 152,156 control chromosomes in the GnomAD database, including 54,320 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 0.84 (54320 hom., cov: 31)
• Consequence: PTK2B NM_173176.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.370

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=-0.89).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.866 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PTK2B	NM_173176.3	c.204+6510A>G		intron_variant		ENST00000346049.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PTK2B	ENST00000346049.10	c.204+6510A>G		intron_variant		1	NM_173176.3	A1

Frequencies

GnomAD3 genomes AF: 0.841 AC: 127880 AN: 152038 Hom.: 54272 Cov.: 31

Gnomad AFR AF: 0.856

Gnomad AMI AF: 0.850

Gnomad AMR AF: 0.733

Gnomad ASJ AF: 0.938

Gnomad EAS AF: 0.541

Gnomad SAS AF: 0.878

Gnomad FIN AF: 0.830

Gnomad MID AF: 0.949

Gnomad NFE AF: 0.872

Gnomad OTH AF: 0.856

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

GnomAD4 genome AF: 0.841 AC: 127985 AN: 152156 Hom.: 54320 Cov.: 31 AF XY: 0.835 AC XY: 62099 AN XY: 74354

Gnomad4 AFR AF: 0.857

Gnomad4 AMR AF: 0.733

Gnomad4 ASJ AF: 0.938

Gnomad4 EAS AF: 0.542

Gnomad4 SAS AF: 0.877

Gnomad4 FIN AF: 0.830

Gnomad4 NFE AF: 0.872

Gnomad4 OTH AF: 0.858

Alfa AF: 0.846 Hom.: 8629

Bravo AF: 0.830

Asia WGS AF: 0.744 AC: 2591 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	2.8
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: rs11994882; hg19: chr8-27261815;