rs11782673

Variant names:

• chr8-27408370-A-G
• rs11782673
• NM_173176.3:c.204+10582A>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.204+10582A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.135 in 152,260 control chromosomes in the GnomAD database, including 1,690 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 0.14 (1690 hom., cov: 33)
• Consequence: PTK2B NM_173176.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.347
• Publications: 8 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=-0.76).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.198 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PTK2B	NM_173176.3	c.204+10582A>G		intron_variant	Intron 2 of 30	ENST00000346049.10	NP_775268.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PTK2B	ENST00000346049.10	c.204+10582A>G		intron_variant	Intron 2 of 30	1	NM_173176.3	ENSP00000332816.6

Frequencies

GnomAD3 genomes AF: 0.135 AC: 20580 AN: 152142 Hom.: 1684 Cov.: 33

Gnomad AFR AF: 0.0511

Gnomad AMI AF: 0.0989

Gnomad AMR AF: 0.203

Gnomad ASJ AF: 0.159

Gnomad EAS AF: 0.0899

Gnomad SAS AF: 0.0666

Gnomad FIN AF: 0.207

Gnomad MID AF: 0.104

Gnomad NFE AF: 0.167

Gnomad OTH AF: 0.152

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

GnomAD4 genome AF: 0.135 AC: 20609 AN: 152260 Hom.: 1690 Cov.: 33 AF XY: 0.136 AC XY: 10097 AN XY: 74452

African (AFR) AF: 0.0514 AC: 2137 AN: 41582

American (AMR) AF: 0.204 AC: 3114 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.159 AC: 553 AN: 3468

East Asian (EAS) AF: 0.0899 AC: 465 AN: 5174

South Asian (SAS) AF: 0.0673 AC: 325 AN: 4828

European-Finnish (FIN) AF: 0.207 AC: 2198 AN: 10602

Middle Eastern (MID) AF: 0.0986 AC: 29 AN: 294

European-Non Finnish (NFE) AF: 0.167 AC: 11381 AN: 67998

Other (OTH) AF: 0.150 AC: 317 AN: 2112

Alfa AF: 0.0219 Hom.: 281

Bravo AF: 0.134

Asia WGS AF: 0.0850 AC: 297 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	12
DANN	Benign	0.85
PhyloP100		0.35
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: rs11782673; hg19: chr8-27265887;