rs2251430

Variant names:

• chr8-27451332-A-G
• rs2251430
• NM_173176.3:c.2524-153A>G

Your query was ambiguous. Multiple possible variants found:

• chr8-27451332-A-G
• chr8-27451332-A-T

Variant summary

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

The NM_173176.3(PTK2B):​c.2524-153A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.852 in 152,148 control chromosomes in the GnomAD database, including 55,681 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 0.85 (55681 hom., cov: 32)
• Consequence: PTK2B NM_173176.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.47
• Publications: 12 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=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.879 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PTK2B	NM_173176.3	c.2524-153A>G		intron_variant	Intron 26 of 30	ENST00000346049.10	NP_775268.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PTK2B	ENST00000346049.10	c.2524-153A>G		intron_variant	Intron 26 of 30	1	NM_173176.3	ENSP00000332816.6

Frequencies

GnomAD3 genomes AF: 0.852 AC: 129605 AN: 152030 Hom.: 55640 Cov.: 32

Gnomad AFR AF: 0.887

Gnomad AMI AF: 0.911

Gnomad AMR AF: 0.820

Gnomad ASJ AF: 0.936

Gnomad EAS AF: 0.525

Gnomad SAS AF: 0.846

Gnomad FIN AF: 0.828

Gnomad MID AF: 0.946

Gnomad NFE AF: 0.862

Gnomad OTH AF: 0.874

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

GnomAD4 genome AF: 0.852 AC: 129698 AN: 152148 Hom.: 55681 Cov.: 32 AF XY: 0.848 AC XY: 63043 AN XY: 74370

African (AFR) AF: 0.887 AC: 36818 AN: 41522

American (AMR) AF: 0.820 AC: 12539 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.936 AC: 3249 AN: 3472

East Asian (EAS) AF: 0.525 AC: 2691 AN: 5126

South Asian (SAS) AF: 0.845 AC: 4074 AN: 4824

European-Finnish (FIN) AF: 0.828 AC: 8776 AN: 10596

Middle Eastern (MID) AF: 0.942 AC: 277 AN: 294

European-Non Finnish (NFE) AF: 0.862 AC: 58593 AN: 67998

Other (OTH) AF: 0.875 AC: 1850 AN: 2114

Alfa AF: 0.862 Hom.: 57725

Bravo AF: 0.855

Asia WGS AF: 0.727 AC: 2529 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.21
DANN	Benign	0.34
PhyloP100		-1.5
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: rs2251430; hg19: chr8-27308849; COSMIC: COSV57769195; COSMIC: COSV57769195;