NM_018936.4:c.79C>G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_018936.4(PCDHB2):​c.79C>G​(p.Gln27Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000616 in 1,461,008 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000062 ( 0 hom. )

Consequence

PCDHB2
NM_018936.4 missense

Scores

19

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.105
Variant links:
Genes affected
PCDHB2 (HGNC:8687): (protocadherin beta 2) This gene is a member of the protocadherin beta gene cluster, one of three related gene clusters tandemly linked on chromosome five. The gene clusters demonstrate an unusual genomic organization similar to that of B-cell and T-cell receptor gene clusters. The beta cluster contains 16 genes and 3 pseudogenes, each encoding 6 extracellular cadherin domains and a cytoplasmic tail that deviates from others in the cadherin superfamily. The extracellular domains interact in a homophilic manner to specify differential cell-cell connections. Unlike the alpha and gamma clusters, the transcripts from these genes are made up of only one large exon, not sharing common 3' exons as expected. These neural cadherin-like cell adhesion proteins are integral plasma membrane proteins. Their specific functions are unknown but they most likely play a critical role in the establishment and function of specific cell-cell neural connections. [provided by RefSeq, Jul 2008]
PCDHB1-AS1 (HGNC:56111): (PCDHB1 antisense RNA 1)

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.036485434).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
PCDHB2NM_018936.4 linkc.79C>G p.Gln27Glu missense_variant Exon 1 of 1 ENST00000194155.7 NP_061759.1 Q9Y5E7Q4KMG6
PCDHB@ n.141094869C>G intragenic_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
PCDHB2ENST00000194155.7 linkc.79C>G p.Gln27Glu missense_variant Exon 1 of 1 6 NM_018936.4 ENSP00000194155.4 Q9Y5E7

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.0000120
AC:
3
AN:
250678
Hom.:
0
AF XY:
0.00000738
AC XY:
1
AN XY:
135506
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 SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.000491
GnomAD4 exome
AF:
0.00000616
AC:
9
AN:
1461008
Hom.:
0
Cov.:
31
AF XY:
0.00000550
AC XY:
4
AN XY:
726818
show subpopulations
Gnomad4 AFR exome
AF:
0.0000299
Gnomad4 AMR exome
AF:
0.0000225
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:
0.00000360
Gnomad4 OTH exome
AF:
0.0000497
GnomAD4 genome
Cov.:
32
ExAC
AF:
0.0000165
AC:
2
EpiCase
AF:
0.00
EpiControl
AF:
0.0000593

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Aug 12, 2022
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.79C>G (p.Q27E) alteration is located in exon 1 (coding exon 1) of the PCDHB2 gene. This alteration results from a C to G substitution at nucleotide position 79, causing the glutamine (Q) at amino acid position 27 to be replaced by a glutamic acid (E). 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
0.064
BayesDel_addAF
Benign
-0.28
T
BayesDel_noAF
Benign
-0.64
CADD
Benign
11
DANN
Benign
0.73
DEOGEN2
Benign
0.0014
T
Eigen
Benign
-0.83
Eigen_PC
Benign
-0.68
FATHMM_MKL
Benign
0.019
N
LIST_S2
Benign
0.19
T
M_CAP
Benign
0.0042
T
MetaRNN
Benign
0.036
T
MetaSVM
Benign
-0.99
T
MutationAssessor
Benign
0.0
N
PrimateAI
Benign
0.27
T
PROVEAN
Benign
-0.66
N
REVEL
Benign
0.064
Sift
Benign
1.0
T
Sift4G
Benign
1.0
T
Polyphen
0.0
B
Vest4
0.14
MutPred
0.33
Loss of MoRF binding (P = 0.1061);
MVP
0.17
ClinPred
0.021
T
GERP RS
1.5
Varity_R
0.081
gMVP
0.14

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.

Other links and lift over

dbSNP: rs782229850; hg19: chr5-140474453; API