Genetic Variant NM_001173523.2:c.718C>G (chr4-30722140-C-G) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001173523.2(PCDH7):c.718C>G(p.Arg240Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000762 in 1,312,672 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R240L) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 7.6e-7 ( 0 hom. )

Consequence

PCDH7
NM_001173523.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.18

Publications

0 publications found

Variant links:

Genes affected

PCDH7 (HGNC:8659): (protocadherin 7) This gene belongs to the protocadherin gene family, a subfamily of the cadherin superfamily. The gene encodes a protein with an extracellular domain containing 7 cadherin repeats. The gene product is an integral membrane protein that is thought to function in cell-cell recognition and adhesion. Alternative splicing yields isoforms with unique cytoplasmic tails. [provided by RefSeq, Jul 2008]

PCDH7 links:

ENSG00000286596 (HGNC:58750):

ENSG00000286596 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.19546804).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001173523.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PCDH7	NM_001173523.2	MANE Select	c.718C>G	p.Arg240Gly	missense	Exon 1 of 3	NP_001166994.1	A0A8Q3SI70
PCDH7	NM_032457.4		c.718C>G	p.Arg240Gly	missense	Exon 1 of 3	NP_115833.2	A0A8V8TM73
PCDH7	NM_002589.4		c.718C>G	p.Arg240Gly	missense	Exon 1 of 2	NP_002580.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PCDH7	ENST00000695919.1	MANE Select	c.718C>G	p.Arg240Gly	missense	Exon 1 of 3	ENSP00000512266.1	A0A8Q3SI70
PCDH7	ENST00000361762.3	TSL:1	c.718C>G	p.Arg240Gly	missense	Exon 1 of 2	ENSP00000355243.2	O60245-1
PCDH7	ENST00000621961.2	TSL:5	c.718C>G	p.Arg240Gly	missense	Exon 1 of 4	ENSP00000484874.2	A0A087X2C4

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

7.62e-7

AC:

AN:

1312672

Hom.:

Cov.:

AF XY:

0.00000156

AC XY:

AN XY:

641052

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

26978

American (AMR)

AF:

0.00

AC:

AN:

26448

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

20092

East Asian (EAS)

AF:

0.00

AC:

AN:

31720

South Asian (SAS)

AF:

0.0000147

AC:

AN:

67902

European-Finnish (FIN)

AF:

0.00

AC:

AN:

36522

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5256

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1043348

Other (OTH)

AF:

0.00

AC:

AN:

54406

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.575

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ExAC

AF:

0.00000990

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Uncertain

0.065

BayesDel_noAF

Benign

-0.14

CADD

Uncertain

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.032

Eigen

Benign

-0.10

Eigen_PC

Benign

0.023

FATHMM_MKL

Uncertain

0.91

LIST_S2

Benign

0.85

M_CAP

Uncertain

0.29

MetaRNN

Benign

0.20

MetaSVM

Benign

-0.91

MutationAssessor

Benign

-0.29

PhyloP100

1.2

PrimateAI

Pathogenic

0.85

PROVEAN

Benign

-0.68

REVEL

Benign

0.24

Sift

Benign

0.080

Sift4G

Uncertain

0.0070

Polyphen

0.61

Vest4

0.36

MutPred

0.43

Loss of solvent accessibility (P = 0.0044)

MVP

0.30

ClinPred

0.90

GERP RS

4.5

PromoterAI

-0.0037

Neutral

(source)

Varity_R

0.25

gMVP

0.56

Mutation Taster

=19/81

disease causing

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over