6-43129099-G-C

Variant names:

• chr6-43129099-G-C
• rs986327432
• NM_002821.5:c.202G>C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_002821.5(PTK7):​c.202G>C​(p.Asp68His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: PTK7 NM_002821.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.483

Genes affected

PTK7 (HGNC:9618): (protein tyrosine kinase 7 (inactive)) This gene encodes a member of the receptor protein tyrosine kinase family of proteins that transduce extracellular signals across the cell membrane. The encoded protein lacks detectable catalytic tyrosine kinase activity, is involved in the Wnt signaling pathway and plays a role in multiple cellular processes including polarity and adhesion. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Jul 2012]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.41059682).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PTK7	NM_002821.5	c.202G>C	p.Asp68His	missense_variant	Exon 2 of 20	ENST00000230419.9	NP_002812.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PTK7	ENST00000230419.9	c.202G>C	p.Asp68His	missense_variant	Exon 2 of 20	1	NM_002821.5	ENSP00000230419.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.32
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.40
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Benign	0.31	T;T;.;.;.;.;.
Eigen	Benign	-0.13
Eigen_PC	Benign	-0.32
FATHMM_MKL	Benign	0.45	N
LIST_S2	Uncertain	0.94	D;D;D;D;D;D;D
M_CAP	Benign	0.053	D
MetaRNN	Benign	0.41	T;T;T;T;T;T;T
MetaSVM	Benign	-0.79	T
MutationAssessor	Pathogenic	3.4	M;.;.;M;M;M;.
PrimateAI	Benign	0.44	T
PROVEAN	Benign	-1.6	N;D;D;N;N;N;N
REVEL	Benign	0.21
Sift	Uncertain	0.0060	D;D;D;D;D;D;D
Sift4G	Uncertain	0.0020	D;D;D;D;D;D;D
Polyphen		0.87	P;.;D;P;P;P;.
Vest4		0.40
MutPred		0.68		Gain of catalytic residue at G69 (P = 0.0973);Gain of catalytic residue at G69 (P = 0.0973);Gain of catalytic residue at G69 (P = 0.0973);Gain of catalytic residue at G69 (P = 0.0973);Gain of catalytic residue at G69 (P = 0.0973);Gain of catalytic residue at G69 (P = 0.0973);.;
MVP		0.52
MPC		1.1
ClinPred		0.97	D
GERP RS		1.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.6
Varity_R		0.096
gMVP		0.62

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs986327432; hg19: chr6-43096837;