NM_018900.4:c.2394+93408A>T
Variant names:
Variant summary
Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong
The NM_018900.4(PCDHA1):c.2394+93408A>T variant causes a intron change. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.
Frequency
Genomes: 𝑓 0.0 ( 0 hom., cov: 33)
Exomes 𝑓: 0.0000081 ( 0 hom. )
Failed GnomAD Quality Control
Consequence
PCDHA1
NM_018900.4 intron
NM_018900.4 intron
Scores
2
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: 6.00
Publications
4 publications found
Genes affected
PCDHA1 (HGNC:8663): (protocadherin alpha 1) This gene is a member of the protocadherin alpha gene cluster, one of three related gene clusters tandemly linked on chromosome five that demonstrate an unusual genomic organization similar to that of B-cell and T-cell receptor gene clusters. The alpha gene cluster is composed of 15 cadherin superfamily genes related to the mouse CNR genes and consists of 13 highly similar and 2 more distantly related coding sequences. The tandem array of 15 N-terminal exons, or variable exons, are followed by downstream C-terminal exons, or constant exons, which are shared by all genes in the cluster. The large, uninterrupted N-terminal exons each encode six cadherin ectodomains while the C-terminal exons encode the cytoplasmic domain. These neural cadherin-like cell adhesion proteins are integral plasma membrane proteins that most likely play a critical role in the establishment and function of specific cell-cell connections in the brain. Alternative splicing has been observed and additional variants have been suggested but their full-length nature has yet to be determined. [provided by RefSeq, Jul 2008]
PCDHA3 (HGNC:8669): (protocadherin alpha 3) This gene is a member of the protocadherin alpha gene cluster, one of three related gene clusters tandemly linked on chromosome five that demonstrate an unusual genomic organization similar to that of B-cell and T-cell receptor gene clusters. The alpha gene cluster is composed of 15 cadherin superfamily genes related to the mouse CNR genes and consists of 13 highly similar and 2 more distantly related coding sequences. The tandem array of 15 N-terminal exons, or variable exons, are followed by downstream C-terminal exons, or constant exons, which are shared by all genes in the cluster. The large, uninterrupted N-terminal exons each encode six cadherin ectodomains while the C-terminal exons encode the cytoplasmic domain. These neural cadherin-like cell adhesion proteins are integral plasma membrane proteins that most likely play a critical role in the establishment and function of specific cell-cell connections in the brain. Alternative splicing has been observed and additional variants have been suggested but their full-length nature has yet to be determined. [provided by RefSeq, Jul 2008]
PCDHA6 (HGNC:8672): (protocadherin alpha 6) This gene is a member of the protocadherin alpha gene cluster, one of three related gene clusters tandemly linked on chromosome five that demonstrate an unusual genomic organization similar to that of B-cell and T-cell receptor gene clusters. The alpha gene cluster is composed of 15 cadherin superfamily genes related to the mouse CNR genes and consists of 13 highly similar and 2 more distantly related coding sequences. The tandem array of 15 N-terminal exons, or variable exons, are followed by downstream C-terminal exons, or constant exons, which are shared by all genes in the cluster. The large, uninterrupted N-terminal exons each encode six cadherin ectodomains while the C-terminal exons encode the cytoplasmic domain. These neural cadherin-like cell adhesion proteins are integral plasma membrane proteins that most likely play a critical role in the establishment and function of specific cell-cell connections in the brain. Alternative splicing has been observed and additional variants have been suggested but their full-length nature has yet to be determined. [provided by RefSeq, Jul 2008]
PCDHA8 (HGNC:8674): (protocadherin alpha 8) This gene is a member of the protocadherin alpha gene cluster, one of three related gene clusters tandemly linked on chromosome five that demonstrate an unusual genomic organization similar to that of B-cell and T-cell receptor gene clusters. The alpha gene cluster is composed of 15 cadherin superfamily genes related to the mouse CNR genes and consists of 13 highly similar and 2 more distantly related coding sequences. The tandem array of 15 N-terminal exons, or variable exons, are followed by downstream C-terminal exons, or constant exons, which are shared by all genes in the cluster. The large, uninterrupted N-terminal exons each encode six cadherin ectodomains while the C-terminal exons encode the cytoplasmic domain. These neural cadherin-like cell adhesion proteins are integral plasma membrane proteins that most likely play a critical role in the establishment and function of specific cell-cell connections in the brain. Alternative splicing has been observed and additional variants have been suggested but their full-length nature has yet to be determined. [provided by RefSeq, Jul 2008]
PCDHA9 (HGNC:8675): (protocadherin alpha 9) This gene is a member of the protocadherin alpha gene cluster, one of three related gene clusters tandemly linked on chromosome five that demonstrate an unusual genomic organization similar to that of B-cell and T-cell receptor gene clusters. The alpha gene cluster is composed of 15 cadherin superfamily genes related to the mouse CNR genes and consists of 13 highly similar and 2 more distantly related coding sequences. The tandem array of 15 N-terminal exons, or variable exons, are followed by downstream C-terminal exons, or constant exons, which are shared by all genes in the cluster. The large, uninterrupted N-terminal exons each encode six cadherin ectodomains while the C-terminal exons encode the cytoplasmic domain. These neural cadherin-like cell adhesion proteins are integral plasma membrane proteins that most likely play a critical role in the establishment and function of specific cell-cell connections in the brain. Alternative splicing has been observed and additional variants have been suggested but their full-length nature has yet to be determined. [provided by RefSeq, Jul 2008]
PCDHA11 (HGNC:8665): (protocadherin alpha 11) This gene is a member of the protocadherin alpha gene cluster, one of three related gene clusters tandemly linked on chromosome five that demonstrate an unusual genomic organization similar to that of B-cell and T-cell receptor gene clusters. The alpha gene cluster is composed of 15 cadherin superfamily genes related to the mouse CNR genes and consists of 13 highly similar and 2 more distantly related coding sequences. The tandem array of 15 N-terminal exons, or variable exons, are followed by downstream C-terminal exons, or constant exons, which are shared by all genes in the cluster. The large, uninterrupted N-terminal exons each encode six cadherin ectodomains while the C-terminal exons encode the cytoplasmic domain. These neural cadherin-like cell adhesion proteins are integral plasma membrane proteins that most likely play a critical role in the establishment and function of specific cell-cell connections in the brain. Alternative splicing has been observed and additional variants have been suggested but their full-length nature has yet to be determined. [provided by RefSeq, Jul 2008]
PCDHA10 (HGNC:8664): (protocadherin alpha 10) This gene is a member of the protocadherin alpha gene cluster, one of three related gene clusters tandemly linked on chromosome five that demonstrate an unusual genomic organization similar to that of B-cell and T-cell receptor gene clusters. The alpha gene cluster is composed of 15 cadherin superfamily genes related to the mouse CNR genes and consists of 13 highly similar and 2 more distantly related coding sequences. The tandem array of 15 N-terminal exons, or variable exons, are followed by downstream C-terminal exons, or constant exons, which are shared by all genes in the cluster. The large, uninterrupted N-terminal exons each encode six cadherin ectodomains while the C-terminal exons encode the cytoplasmic domain. These neural cadherin-like cell adhesion proteins are integral plasma membrane proteins that most likely play a critical role in the establishment and function of specific cell-cell connections in the brain. Alternative splicing has been observed and additional variants have been suggested but their full-length nature has yet to be determined. [provided by RefSeq, Jul 2008]
PCDHA2 (HGNC:8668): (protocadherin alpha 2) This gene is a member of the protocadherin alpha gene cluster, one of three related gene clusters tandemly linked on chromosome five that demonstrate an unusual genomic organization similar to that of B-cell and T-cell receptor gene clusters. The alpha gene cluster is composed of 15 cadherin superfamily genes related to the mouse CNR genes and consists of 13 highly similar and 2 more distantly related coding sequences. The tandem array of 15 N-terminal exons, or variable exons, are followed by downstream C-terminal exons, or constant exons, which are shared by all genes in the cluster. The large, uninterrupted N-terminal exons each encode six cadherin ectodomains while the C-terminal exons encode the cytoplasmic domain. These neural cadherin-like cell adhesion proteins are integral plasma membrane proteins that most likely play a critical role in the establishment and function of specific cell-cell connections in the brain. Alternative splicing has been observed and additional variants have been suggested but their full-length nature has yet to be determined. [provided by RefSeq, Jul 2008]
PCDHA4 (HGNC:8670): (protocadherin alpha 4) This gene is a member of the protocadherin alpha gene cluster, one of three related gene clusters tandemly linked on chromosome five that demonstrate an unusual genomic organization similar to that of B-cell and T-cell receptor gene clusters. The alpha gene cluster is composed of 15 cadherin superfamily genes related to the mouse CNR genes and consists of 13 highly similar and 2 more distantly related coding sequences. The tandem array of 15 N-terminal exons, or variable exons, are followed by downstream C-terminal exons, or constant exons, which are shared by all genes in the cluster. The large, uninterrupted N-terminal exons each encode six cadherin ectodomains while the C-terminal exons encode the cytoplasmic domain. These neural cadherin-like cell adhesion proteins are integral plasma membrane proteins that most likely play a critical role in the establishment and function of specific cell-cell connections in the brain. Alternative splicing has been observed and additional variants have been suggested but their full-length nature has yet to be determined. [provided by RefSeq, Jul 2008]
PCDHA12 (HGNC:8666): (protocadherin alpha 12) This gene is a member of the protocadherin alpha gene cluster, one of three related gene clusters tandemly linked on chromosome five that demonstrate an unusual genomic organization similar to that of B-cell and T-cell receptor gene clusters. The alpha gene cluster is composed of 15 cadherin superfamily genes related to the mouse CNR genes and consists of 13 highly similar and 2 more distantly related coding sequences. The tandem array of 15 N-terminal exons, or variable exons, are followed by downstream C-terminal exons, or constant exons, which are shared by all genes in the cluster. The large, uninterrupted N-terminal exons each encode six cadherin ectodomains while the C-terminal exons encode the cytoplasmic domain. These neural cadherin-like cell adhesion proteins are integral plasma membrane proteins that most likely play a critical role in the establishment and function of specific cell-cell connections in the brain. Alternative splicing has been observed and additional variants have been suggested but their full-length nature has yet to be determined. [provided by RefSeq, Jul 2008]
PCDHA7 (HGNC:8673): (protocadherin alpha 7) This gene is a member of the protocadherin alpha gene cluster, one of three related gene clusters tandemly linked on chromosome five that demonstrate an unusual genomic organization similar to that of B-cell and T-cell receptor gene clusters. The alpha gene cluster is composed of 15 cadherin superfamily genes related to the mouse CNR genes and consists of 13 highly similar and 2 more distantly related coding sequences. The tandem array of 15 N-terminal exons, or variable exons, are followed by downstream C-terminal exons, or constant exons, which are shared by all genes in the cluster. The large, uninterrupted N-terminal exons each encode six cadherin ectodomains while the C-terminal exons encode the cytoplasmic domain. These neural cadherin-like cell adhesion proteins are integral plasma membrane proteins that most likely play a critical role in the establishment and function of specific cell-cell connections in the brain. Alternative splicing has been observed and additional variants have been suggested but their full-length nature has yet to be determined. [provided by RefSeq, Jul 2008]
PCDHA5 (HGNC:8671): (protocadherin alpha 5) This gene is a member of the protocadherin alpha gene cluster, one of three related gene clusters tandemly linked on chromosome five that demonstrate an unusual genomic organization similar to that of B-cell and T-cell receptor gene clusters. The alpha gene cluster is composed of 15 cadherin superfamily genes related to the mouse CNR genes and consists of 13 highly similar and 2 more distantly related coding sequences. The tandem array of 15 N-terminal exons, or variable exons, are followed by downstream C-terminal exons, or constant exons, which are shared by all genes in the cluster. The large, uninterrupted N-terminal exons each encode six cadherin ectodomains while the C-terminal exons encode the cytoplasmic domain. These neural cadherin-like cell adhesion proteins are integral plasma membrane proteins that most likely play a critical role in the establishment and function of specific cell-cell connections in the brain. Alternative splicing has been observed and additional variants have been suggested but their full-length nature has yet to be determined. [provided by RefSeq, Jul 2008]
PCDHA13 (HGNC:8667): (protocadherin alpha 13) This gene is a member of the protocadherin alpha gene cluster, one of three related gene clusters tandemly linked on chromosome five that demonstrate an unusual genomic organization similar to that of B-cell and T-cell receptor gene clusters. The alpha gene cluster is composed of 15 cadherin superfamily genes related to the mouse CNR genes and consists of 13 highly similar and 2 more distantly related coding sequences. The tandem array of 15 N-terminal exons, or variable exons, are followed by downstream C-terminal exons, or constant exons, which are shared by all genes in the cluster. The large, uninterrupted N-terminal exons each encode six cadherin ectodomains while the C-terminal exons encode the cytoplasmic domain. These neural cadherin-like cell adhesion proteins are integral plasma membrane proteins that most likely play a critical role in the establishment and function of specific cell-cell connections in the brain. Alternative splicing has been observed and additional variants have been suggested but their full-length nature has yet to be determined. [provided by RefSeq, Jul 2008]
Genome browser will be placed here
ACMG classification
Classification was made for transcript
Our verdict: Likely_benign. The variant received -4 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.6).
Transcripts
RefSeq
| Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|
| PCDHA1 | NM_018900.4 | c.2394+93408A>T | intron_variant | Intron 1 of 3 | ENST00000504120.4 | NP_061723.1 | ||
| PCDHA3 | NM_018906.3 | c.2394+78501A>T | intron_variant | Intron 1 of 3 | ENST00000522353.3 | NP_061729.1 | ||
| PCDHA6 | NM_018909.4 | c.2394+51607A>T | intron_variant | Intron 1 of 3 | ENST00000529310.6 | NP_061732.1 | ||
| PCDHA8 | NM_018911.3 | c.2394+38377A>T | intron_variant | Intron 1 of 3 | ENST00000531613.2 | NP_061734.1 | ||
| PCDHA9 | NM_031857.2 | c.2394+31203A>T | intron_variant | Intron 1 of 3 | ENST00000532602.2 | NP_114063.1 | ||
| PCDHA11 | NM_018902.5 | c.2391+10598A>T | intron_variant | Intron 1 of 3 | ENST00000398640.7 | NP_061725.1 | ||
| PCDHA10 | NM_018901.4 | c.2388+23656A>T | intron_variant | Intron 1 of 3 | ENST00000307360.6 | NP_061724.1 | ||
| PCDHA2 | NM_018905.3 | c.2388+84740A>T | intron_variant | Intron 1 of 3 | ENST00000526136.2 | NP_061728.1 | ||
| PCDHA4 | NM_018907.4 | c.2385+72520A>T | intron_variant | Intron 1 of 3 | ENST00000530339.2 | NP_061730.1 | ||
| PCDHA12 | NM_018903.4 | c.2367+4253A>T | intron_variant | Intron 1 of 3 | ENST00000398631.3 | NP_061726.1 | ||
| PCDHA7 | NM_018910.3 | c.2355+45354A>T | intron_variant | Intron 1 of 3 | ENST00000525929.2 | NP_061733.1 | ||
| PCDHA5 | NM_018908.3 | c.2352+57965A>T | intron_variant | Intron 1 of 3 | ENST00000529859.2 | NP_061731.1 | ||
| PCDHA13 | NM_018904.3 | c.-177A>T | upstream_gene_variant | ENST00000289272.3 | NP_061727.1 |
Ensembl
| Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
|---|---|---|---|---|---|---|---|---|---|---|
| PCDHA1 | ENST00000504120.4 | c.2394+93408A>T | intron_variant | Intron 1 of 3 | 1 | NM_018900.4 | ENSP00000420840.3 | |||
| PCDHA3 | ENST00000522353.3 | c.2394+78501A>T | intron_variant | Intron 1 of 3 | 1 | NM_018906.3 | ENSP00000429808.2 | |||
| PCDHA6 | ENST00000529310.6 | c.2394+51607A>T | intron_variant | Intron 1 of 3 | 1 | NM_018909.4 | ENSP00000433378.1 | |||
| PCDHA8 | ENST00000531613.2 | c.2394+38377A>T | intron_variant | Intron 1 of 3 | 1 | NM_018911.3 | ENSP00000434655.1 | |||
| PCDHA9 | ENST00000532602.2 | c.2394+31203A>T | intron_variant | Intron 1 of 3 | 1 | NM_031857.2 | ENSP00000436042.2 | |||
| PCDHA11 | ENST00000398640.7 | c.2391+10598A>T | intron_variant | Intron 1 of 3 | 1 | NM_018902.5 | ENSP00000381636.3 | |||
| PCDHA10 | ENST00000307360.6 | c.2388+23656A>T | intron_variant | Intron 1 of 3 | 1 | NM_018901.4 | ENSP00000304234.5 | |||
| PCDHA2 | ENST00000526136.2 | c.2388+84740A>T | intron_variant | Intron 1 of 3 | 1 | NM_018905.3 | ENSP00000431748.1 | |||
| PCDHA4 | ENST00000530339.2 | c.2385+72520A>T | intron_variant | Intron 1 of 3 | 1 | NM_018907.4 | ENSP00000435300.1 | |||
| PCDHA12 | ENST00000398631.3 | c.2367+4253A>T | intron_variant | Intron 1 of 3 | 1 | NM_018903.4 | ENSP00000381628.2 | |||
| PCDHA7 | ENST00000525929.2 | c.2355+45354A>T | intron_variant | Intron 1 of 3 | 1 | NM_018910.3 | ENSP00000436426.1 | |||
| PCDHA5 | ENST00000529859.2 | c.2352+57965A>T | intron_variant | Intron 1 of 3 | 1 | NM_018908.3 | ENSP00000436557.1 | |||
| PCDHA13 | ENST00000289272.3 | c.-177A>T | upstream_gene_variant | 1 | NM_018904.3 | ENSP00000289272.2 |
Frequencies
GnomAD3 genomes 0.00 AC: 0AN: 152036Hom.: 0 Cov.: 33
GnomAD3 genomes
AF:
AC:
0
AN:
152036
Hom.:
Cov.:
33
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000810 AC: 8AN: 987126Hom.: 0 Cov.: 13 AF XY: 0.00000814 AC XY: 4AN XY: 491162 show subpopulations
GnomAD4 exome
Data not reliable, filtered out with message: AS_VQSR
AF:
AC:
8
AN:
987126
Hom.:
Cov.:
13
AF XY:
AC XY:
4
AN XY:
491162
show subpopulations
African (AFR)
AF:
AC:
0
AN:
22904
American (AMR)
AF:
AC:
0
AN:
21502
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
17178
East Asian (EAS)
AF:
AC:
0
AN:
35100
South Asian (SAS)
AF:
AC:
0
AN:
56472
European-Finnish (FIN)
AF:
AC:
0
AN:
37906
Middle Eastern (MID)
AF:
AC:
0
AN:
2954
European-Non Finnish (NFE)
AF:
AC:
8
AN:
749416
Other (OTH)
AF:
AC:
0
AN:
43694
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.556
Heterozygous variant carriers
0
1
2
2
3
4
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Age Distribution
Exome Het
Variant carriers
0
2
4
6
8
10
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
GnomAD4 genome 0.00 AC: 0AN: 152036Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0AN XY: 74248
GnomAD4 genome
Data not reliable, filtered out with message: AC0
AF:
AC:
0
AN:
152036
Hom.:
Cov.:
33
AF XY:
AC XY:
0
AN XY:
74248
African (AFR)
AF:
AC:
0
AN:
41384
American (AMR)
AF:
AC:
0
AN:
15278
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
3472
East Asian (EAS)
AF:
AC:
0
AN:
5184
South Asian (SAS)
AF:
AC:
0
AN:
4834
European-Finnish (FIN)
AF:
AC:
0
AN:
10572
Middle Eastern (MID)
AF:
AC:
0
AN:
316
European-Non Finnish (NFE)
AF:
AC:
0
AN:
67992
Other (OTH)
AF:
AC:
0
AN:
2092
Alfa
AF:
Hom.:
ClinVar
Not reported inComputational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
DANN
Benign
PhyloP100
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
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.