chrX-91878392-G-A
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Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_032968.5(PCDH11X):c.2152G>A(p.Gly718Arg) variant causes a missense change. The variant allele was found at a frequency of 0.00000182 in 1,096,105 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: not found (cov: 20)
Exomes 𝑓: 0.0000018 ( 0 hom. 0 hem. )
Consequence
PCDH11X
NM_032968.5 missense
NM_032968.5 missense
Scores
2
9
5
Clinical Significance
Conservation
PhyloP100: 6.27
Genes affected
PCDH11X (HGNC:8656): (protocadherin 11 X-linked) This gene belongs to the protocadherin gene family, a subfamily of the cadherin superfamily. The encoded protein consists of an extracellular domain containing 7 cadherin repeats, a transmembrane domain and a cytoplasmic tail that differs from those of the classical cadherins. The gene is located in a major X/Y block of homology and its Y homolog, despite divergence leading to coding region changes, is the most closely related cadherin family member. The protein is thought to play a fundamental role in cell-cell recognition essential for the segmental development and function of the central nervous system. Disruption of this gene may be associated with developmental dyslexia. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jun 2014]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 2 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PCDH11X | NM_032968.5 | c.2152G>A | p.Gly718Arg | missense_variant | 6/11 | ENST00000682573.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PCDH11X | ENST00000682573.1 | c.2152G>A | p.Gly718Arg | missense_variant | 6/11 | NM_032968.5 | P4 |
Frequencies
GnomAD3 genomes Cov.: 20
GnomAD3 genomes
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20
GnomAD3 exomes AF: 0.0000110 AC: 2AN: 181907Hom.: 0 AF XY: 0.0000149 AC XY: 1AN XY: 67145
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GnomAD4 exome AF: 0.00000182 AC: 2AN: 1096105Hom.: 0 Cov.: 29 AF XY: 0.00 AC XY: 0AN XY: 361639
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GnomAD4 genome Cov.: 20
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Dec 21, 2023 | The c.2152G>A (p.G718R) alteration is located in exon 2 (coding exon 2) of the PCDH11X gene. This alteration results from a G to A substitution at nucleotide position 2152, causing the glycine (G) at amino acid position 718 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Pathogenic
D;D;D;D;D;D
M_CAP
Benign
D
MetaRNN
Uncertain
D;D;D;D;D;D
MetaSVM
Uncertain
T
MutationAssessor
Uncertain
M;M;M;M;M;M
MutationTaster
Benign
D;D;D;D;D;D;D;D;D
PrimateAI
Benign
T
PROVEAN
Pathogenic
D;D;D;D;D;D
REVEL
Uncertain
Sift
Uncertain
D;D;D;D;D;D
Sift4G
Uncertain
D;D;D;D;D;D
Polyphen
P;D;B;D;P;P
Vest4
MutPred
Gain of methylation at G718 (P = 0.0741);Gain of methylation at G718 (P = 0.0741);Gain of methylation at G718 (P = 0.0741);Gain of methylation at G718 (P = 0.0741);Gain of methylation at G718 (P = 0.0741);Gain of methylation at G718 (P = 0.0741);
MVP
MPC
2.4
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at