Genetic Variant PCDH7:p.Val243Leu (chr4-30722149-G-T) – 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.727G>T(p.Val243Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000149 in 1,341,282 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. V243M) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000015 ( 0 hom. )

Consequence

PCDH7
NM_001173523.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 7.45

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=0.20605439).

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.727G>T	p.Val243Leu	missense	Exon 1 of 3	NP_001166994.1	A0A8Q3SI70
PCDH7	NM_032457.4		c.727G>T	p.Val243Leu	missense	Exon 1 of 3	NP_115833.2	A0A8V8TM73
PCDH7	NM_002589.4		c.727G>T	p.Val243Leu	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.727G>T	p.Val243Leu	missense	Exon 1 of 3	ENSP00000512266.1	A0A8Q3SI70
PCDH7	ENST00000361762.3	TSL:1	c.727G>T	p.Val243Leu	missense	Exon 1 of 2	ENSP00000355243.2	O60245-1
PCDH7	ENST00000621961.2	TSL:5	c.727G>T	p.Val243Leu	missense	Exon 1 of 4	ENSP00000484874.2	A0A087X2C4

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.0000103

AC:

AN:

96942

AF XY:

0.0000189

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000149

AC:

AN:

1341282

Hom.:

Cov.:

AF XY:

0.00000304

AC XY:

AN XY:

657474

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

28416

American (AMR)

AF:

0.00

AC:

AN:

30358

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

21266

East Asian (EAS)

AF:

0.00

AC:

AN:

33124

South Asian (SAS)

AF:

0.0000279

AC:

AN:

71788

European-Finnish (FIN)

AF:

0.00

AC:

AN:

39620

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5422

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1055638

Other (OTH)

AF:

0.00

AC:

AN:

55650

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.58

BayesDel_addAF

Benign

-0.10

BayesDel_noAF

Benign

-0.20

CADD

Uncertain

(source)

DANN

Benign

0.97

DEOGEN2

Benign

0.028

Eigen

Benign

-0.054

Eigen_PC

Benign

0.17

FATHMM_MKL

Uncertain

0.97

LIST_S2

Uncertain

0.94

M_CAP

Uncertain

0.12

MetaRNN

Benign

0.21

MetaSVM

Benign

-1.1

MutationAssessor

Benign

-0.97

PhyloP100

7.5

PrimateAI

Pathogenic

0.92

PROVEAN

Benign

-0.030

REVEL

Benign

0.24

Sift

Benign

0.46

Sift4G

Benign

0.83

Polyphen

0.27

Vest4

0.49

MutPred

0.38

Loss of sheet (P = 0.0315)

MVP

0.22

ClinPred

0.26

GERP RS

5.3

PromoterAI

0.055

Neutral

(source)

Varity_R

0.19

gMVP

0.37

Mutation Taster

=26/74

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

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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