Variant 13-57633163-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_001040429.3(PCDH17):c.617A>G(p.Gln206Arg) variant causes a missense change. The variant allele was found at a frequency of 0.0000093 in 1,613,320 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 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: 𝑓 0.000013 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000089 ( 0 hom. )

Consequence

PCDH17
NM_001040429.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.11

Variant links:

Genes affected

PCDH17 (HGNC:14267): (protocadherin 17) This gene belongs to the protocadherin gene family, a subfamily of the cadherin superfamily. The encoded protein contains six extracellular cadherin domains, a transmembrane domain, and a cytoplasmic tail differing from those of the classical cadherins. The encoded protein may play a role in the establishment and function of specific cell-cell connections in the brain. [provided by RefSeq, Jul 2008]

PCDH17 links:

ENSG00000278722 (HGNC:):

ENSG00000278722 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.18229112).

BS2

High AC in GnomAdExome4 at 13 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PCDH17	NM_001040429.3 linkuse as main transcript	c.617A>G	p.Gln206Arg	missense_variant	1/4	ENST00000377918.8	NP_001035519.1	O14917-1
PCDH17	XM_005266357.3 linkuse as main transcript	c.617A>G	p.Gln206Arg	missense_variant	2/5		XP_005266414.1	O14917-1
PCDH17	XM_047430276.1 linkuse as main transcript	c.617A>G	p.Gln206Arg	missense_variant	2/5		XP_047286232.1
PCDH17	XM_017020547.2 linkuse as main transcript	c.617A>G	p.Gln206Arg	missense_variant	1/4		XP_016876036.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
PCDH17	ENST00000377918.8 linkuse as main transcript	c.617A>G	p.Gln206Arg	missense_variant	1/4	1	NM_001040429.3	ENSP00000367151.3	O14917-1
PCDH17	ENST00000484979.5 linkuse as main transcript	n.617A>G		non_coding_transcript_exon_variant	1/4	1		ENSP00000432899.1	O14917-2
ENSG00000278722	ENST00000610846.1 linkuse as main transcript	n.413T>C		non_coding_transcript_exon_variant	1/2	4

Frequencies

GnomAD3 genomes

AF:

0.0000132

AC:

AN:

152052

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000890

AC:

AN:

1461268

Hom.:

Cov.:

AF XY:

0.0000110

AC XY:

AN XY:

726956

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000117

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000132

AC:

AN:

152052

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74262

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000113

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 05, 2024

The c.617A>G (p.Q206R) alteration is located in exon 1 (coding exon 1) of the PCDH17 gene. This alteration results from a A to G substitution at nucleotide position 617, causing the glutamine (Q) at amino acid position 206 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.093

BayesDel_addAF

Benign

-0.20

BayesDel_noAF

Benign

-0.53

CADD

Benign

DANN

Benign

0.95

DEOGEN2

Benign

0.21

Eigen

Benign

0.15

Eigen_PC

Benign

0.21

FATHMM_MKL

Uncertain

0.85

LIST_S2

Benign

0.84

M_CAP

Benign

0.032

MetaRNN

Benign

0.18

MetaSVM

Benign

-0.55

MutationAssessor

Benign

1.7

PrimateAI

Uncertain

0.54

PROVEAN

Uncertain

-2.6

REVEL

Benign

0.23

Sift

Benign

0.089

Sift4G

Benign

0.16

Polyphen

0.0080

Vest4

0.13

MutPred

0.50

Gain of catalytic residue at Q206 (P = 0.0021);

MVP

0.50

ClinPred

0.95

GERP RS

4.9

Varity_R

0.56

gMVP

0.57

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over