dbSNP rs867558508: PCDH7:p.Glu181Lys (chr4-30721963-G-A) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001173523.2(PCDH7):c.541G>A(p.Glu181Lys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

PCDH7
NM_001173523.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.68

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 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

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.541G>A	p.Glu181Lys	missense	Exon 1 of 3	NP_001166994.1	A0A8Q3SI70
PCDH7	NM_032457.4		c.541G>A	p.Glu181Lys	missense	Exon 1 of 3	NP_115833.2	A0A8V8TM73
PCDH7	NM_002589.4		c.541G>A	p.Glu181Lys	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.541G>A	p.Glu181Lys	missense	Exon 1 of 3	ENSP00000512266.1	A0A8Q3SI70
PCDH7	ENST00000361762.3	TSL:1	c.541G>A	p.Glu181Lys	missense	Exon 1 of 2	ENSP00000355243.2	O60245-1
PCDH7	ENST00000621961.2	TSL:5	c.541G>A	p.Glu181Lys	missense	Exon 1 of 4	ENSP00000484874.2	A0A087X2C4

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0;AS_VQSR

AF:

0.00

AC:

AN:

1359944

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

671884

African (AFR)

AF:

0.00

AC:

AN:

29092

American (AMR)

AF:

0.00

AC:

AN:

31912

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

23916

East Asian (EAS)

AF:

0.00

AC:

AN:

31922

South Asian (SAS)

AF:

0.00

AC:

AN:

76156

European-Finnish (FIN)

AF:

0.00

AC:

AN:

35842

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5386

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1069094

Other (OTH)

AF:

0.00

AC:

AN:

56624

GnomAD4 genome

Cov.:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.93

BayesDel_addAF

Pathogenic

0.24

BayesDel_noAF

Uncertain

0.11

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.060

Eigen

Uncertain

0.47

Eigen_PC

Uncertain

0.55

FATHMM_MKL

Uncertain

0.90

LIST_S2

Uncertain

0.92

M_CAP

Pathogenic

0.42

MetaRNN

Uncertain

0.47

MetaSVM

Benign

-0.85

MutationAssessor

Benign

0.14

PhyloP100

7.7

PrimateAI

Pathogenic

0.93

PROVEAN

Benign

-2.1

REVEL

Uncertain

0.39

Sift

Uncertain

0.0090

Sift4G

Benign

0.33

Polyphen

0.99

Vest4

0.56

MutPred

0.47

Gain of ubiquitination at E181 (P = 0.0045)

MVP

0.58

ClinPred

0.92

GERP RS

5.2

PromoterAI

0.00060

Neutral

(source)

Varity_R

0.35

gMVP

0.75

Mutation Taster

=15/85

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