8-27405916-G-T

Variant names:

• chr8-27405916-G-T
• rs7000615
• NM_173176.3:c.204+8128G>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.204+8128G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.801 in 152,236 control chromosomes in the GnomAD database, including 49,323 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 0.80 (49323 hom., cov: 33)
• Consequence: PTK2B NM_173176.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.120
• Publications: 18 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=-0.86).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.834 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+8128G>T		intron	N/A	NP_775268.1
	PTK2B	NM_004103.4		c.204+8128G>T		intron	N/A	NP_004094.3
	PTK2B	NM_173174.3		c.204+8128G>T		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+8128G>T		intron	N/A	ENSP00000332816.6
	PTK2B	ENST00000397501.5	TSL:1	c.204+8128G>T		intron	N/A	ENSP00000380638.1
	PTK2B	ENST00000420218.3	TSL:5	c.204+8128G>T		intron	N/A	ENSP00000391995.2

Frequencies

GnomAD3 genomes AF: 0.801 AC: 121862 AN: 152118 Hom.: 49298 Cov.: 33

Gnomad AFR AF: 0.809

Gnomad AMI AF: 0.870

Gnomad AMR AF: 0.700

Gnomad ASJ AF: 0.885

Gnomad EAS AF: 0.521

Gnomad SAS AF: 0.857

Gnomad FIN AF: 0.809

Gnomad MID AF: 0.896

Gnomad NFE AF: 0.829

Gnomad OTH AF: 0.822

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

GnomAD4 genome AF: 0.801 AC: 121939 AN: 152236 Hom.: 49323 Cov.: 33 AF XY: 0.796 AC XY: 59224 AN XY: 74418

African (AFR) AF: 0.809 AC: 33597 AN: 41546

American (AMR) AF: 0.700 AC: 10703 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.885 AC: 3072 AN: 3470

East Asian (EAS) AF: 0.521 AC: 2700 AN: 5184

South Asian (SAS) AF: 0.856 AC: 4122 AN: 4814

European-Finnish (FIN) AF: 0.809 AC: 8570 AN: 10598

Middle Eastern (MID) AF: 0.898 AC: 264 AN: 294

European-Non Finnish (NFE) AF: 0.829 AC: 56379 AN: 68010

Other (OTH) AF: 0.823 AC: 1740 AN: 2114

Alfa AF: 0.818 Hom.: 86258

Bravo AF: 0.791

Asia WGS AF: 0.711 AC: 2474 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	1.7
DANN	Benign	0.28
PhyloP100		-0.12
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: rs7000615; hg19: chr8-27263433;