8-81443402-A-G
Variant summary
Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2
The NM_002677.5(PMP2):āc.395T>Cā(p.Val132Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000589 in 1,595,884 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ā ). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V132D) has been classified as Uncertain significance.
Frequency
Consequence
NM_002677.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -8 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PMP2 | NM_002677.5 | c.395T>C | p.Val132Ala | missense_variant | 4/4 | ENST00000256103.3 | |
PMP2 | NM_001348381.2 | c.*39T>C | 3_prime_UTR_variant | 3/3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PMP2 | ENST00000256103.3 | c.395T>C | p.Val132Ala | missense_variant | 4/4 | 1 | NM_002677.5 | P1 | |
PMP2 | ENST00000519260.1 | c.*39T>C | 3_prime_UTR_variant | 3/3 | 1 | ||||
ENST00000524085.2 | n.298+3309A>G | intron_variant, non_coding_transcript_variant | 5 |
Frequencies
GnomAD3 genomes AF: 0.0000592 AC: 9AN: 152148Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000209 AC: 5AN: 239058Hom.: 0 AF XY: 0.0000232 AC XY: 3AN XY: 129538
GnomAD4 exome AF: 0.0000589 AC: 85AN: 1443736Hom.: 0 Cov.: 27 AF XY: 0.0000585 AC XY: 42AN XY: 718444
GnomAD4 genome AF: 0.0000592 AC: 9AN: 152148Hom.: 0 Cov.: 33 AF XY: 0.0000538 AC XY: 4AN XY: 74316
ClinVar
Submissions by phenotype
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jun 29, 2023 | The c.395T>C (p.V132A) alteration is located in exon 4 (coding exon 4) of the PMP2 gene. This alteration results from a T to C substitution at nucleotide position 395, causing the valine (V) at amino acid position 132 to be replaced by an alanine (A). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Aug 07, 2023 | Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Not Available"; PolyPhen-2: "Benign"; Align-GVGD: "Not Available". The alanine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. ClinVar contains an entry for this variant (Variation ID: 1479286). This variant has not been reported in the literature in individuals affected with PMP2-related conditions. This variant is present in population databases (rs773390955, gnomAD 0.006%). This sequence change replaces valine, which is neutral and non-polar, with alanine, which is neutral and non-polar, at codon 132 of the PMP2 protein (p.Val132Ala). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at