rs7827965

Variant names:

• chr8-27430516-T-C
• rs7827965
• NM_173176.3:c.669+98T>C

Your query was ambiguous. Multiple possible variants found:

• chr8-27430516-T-C
• chr8-27430516-T-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.669+98T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.457 in 1,502,362 control chromosomes in the GnomAD database, including 159,916 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 0.46 (15972 hom., cov: 31)
  • Exomes 𝑓: 0.46 (143944 hom.)
• Consequence: PTK2B NM_173176.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.74
• Publications: 11 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=-0.9).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.536 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PTK2B	NM_173176.3	c.669+98T>C		intron_variant	Intron 7 of 30	ENST00000346049.10	NP_775268.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PTK2B	ENST00000346049.10	c.669+98T>C		intron_variant	Intron 7 of 30	1	NM_173176.3	ENSP00000332816.6

Frequencies

GnomAD3 genomes AF: 0.456 AC: 69103 AN: 151660 Hom.: 15960 Cov.: 31

Gnomad AFR AF: 0.496

Gnomad AMI AF: 0.628

Gnomad AMR AF: 0.422

Gnomad ASJ AF: 0.376

Gnomad EAS AF: 0.254

Gnomad SAS AF: 0.554

Gnomad FIN AF: 0.425

Gnomad MID AF: 0.459

Gnomad NFE AF: 0.454

Gnomad OTH AF: 0.439

GnomAD4 exome AF: 0.457 AC: 617707 AN: 1350584 Hom.: 143944 AF XY: 0.460 AC XY: 310856 AN XY: 675868

African (AFR) AF: 0.489 AC: 15120 AN: 30898

American (AMR) AF: 0.414 AC: 18069 AN: 43686

Ashkenazi Jewish (ASJ) AF: 0.381 AC: 9478 AN: 24846

East Asian (EAS) AF: 0.213 AC: 8292 AN: 38982

South Asian (SAS) AF: 0.578 AC: 48164 AN: 83384

European-Finnish (FIN) AF: 0.425 AC: 22232 AN: 52272

Middle Eastern (MID) AF: 0.481 AC: 2597 AN: 5402

European-Non Finnish (NFE) AF: 0.461 AC: 468040 AN: 1014488

Other (OTH) AF: 0.454 AC: 25715 AN: 56626

GnomAD4 genome AF: 0.456 AC: 69136 AN: 151778 Hom.: 15972 Cov.: 31 AF XY: 0.453 AC XY: 33600 AN XY: 74136

African (AFR) AF: 0.495 AC: 20469 AN: 41358

American (AMR) AF: 0.422 AC: 6430 AN: 15250

Ashkenazi Jewish (ASJ) AF: 0.376 AC: 1304 AN: 3468

East Asian (EAS) AF: 0.254 AC: 1308 AN: 5150

South Asian (SAS) AF: 0.554 AC: 2655 AN: 4792

European-Finnish (FIN) AF: 0.425 AC: 4472 AN: 10534

Middle Eastern (MID) AF: 0.459 AC: 135 AN: 294

European-Non Finnish (NFE) AF: 0.454 AC: 30861 AN: 67922

Other (OTH) AF: 0.443 AC: 932 AN: 2102

Alfa AF: 0.451 Hom.: 20598

Bravo AF: 0.455

Asia WGS AF: 0.451 AC: 1570 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.11
DANN	Benign	0.39
PhyloP100		-2.7
PromoterAI		-0.0084	Neutral
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: rs7827965; hg19: chr8-27288033; COSMIC: COSV57758158; COSMIC: COSV57758158;