8-27407959-A-G

Variant names:

• chr8-27407959-A-G
• rs725787
• NM_173176.3:c.204+10171A>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+10171A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.152 in 152,234 control chromosomes in the GnomAD database, including 2,075 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 (2075 hom., cov: 33)
• Consequence: PTK2B NM_173176.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.901
• Publications: 13 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=-0.89).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.212 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_173176.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PTK2B	NM_173176.3	MANE Select	c.204+10171A>G		intron	N/A	NP_775268.1
	PTK2B	NM_004103.4		c.204+10171A>G		intron	N/A	NP_004094.3
	PTK2B	NM_173174.3		c.204+10171A>G		intron	N/A	NP_775266.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PTK2B	ENST00000346049.10	TSL:1 MANE Select	c.204+10171A>G		intron	N/A	ENSP00000332816.6
	PTK2B	ENST00000397501.5	TSL:1	c.204+10171A>G		intron	N/A	ENSP00000380638.1
	PTK2B	ENST00000420218.3	TSL:5	c.204+10171A>G		intron	N/A	ENSP00000391995.2

Frequencies

GnomAD3 genomes AF: 0.152 AC: 23154 AN: 152116 Hom.: 2069 Cov.: 33

Gnomad AFR AF: 0.0683

Gnomad AMI AF: 0.127

Gnomad AMR AF: 0.217

Gnomad ASJ AF: 0.206

Gnomad EAS AF: 0.0898

Gnomad SAS AF: 0.0693

Gnomad FIN AF: 0.211

Gnomad MID AF: 0.152

Gnomad NFE AF: 0.187

Gnomad OTH AF: 0.174

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

GnomAD4 genome AF: 0.152 AC: 23182 AN: 152234 Hom.: 2075 Cov.: 33 AF XY: 0.152 AC XY: 11300 AN XY: 74418

African (AFR) AF: 0.0685 AC: 2847 AN: 41544

American (AMR) AF: 0.218 AC: 3331 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.206 AC: 715 AN: 3470

East Asian (EAS) AF: 0.0899 AC: 466 AN: 5186

South Asian (SAS) AF: 0.0697 AC: 337 AN: 4832

European-Finnish (FIN) AF: 0.211 AC: 2238 AN: 10592

Middle Eastern (MID) AF: 0.146 AC: 43 AN: 294

European-Non Finnish (NFE) AF: 0.187 AC: 12725 AN: 68002

Other (OTH) AF: 0.173 AC: 364 AN: 2110

Alfa AF: 0.179 Hom.: 3407

Bravo AF: 0.152

Asia WGS AF: 0.0900 AC: 312 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.51
DANN	Benign	0.70
PhyloP100		-0.90
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: rs725787; hg19: chr8-27265476;