rs201407522
Positions:
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 4P and 2B. PM1PM2BP4BS1_Supporting
The NM_032806.6(POMGNT2):c.484G>A(p.Asp162Asn) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000434 in 1,614,108 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).
Frequency
Genomes: 𝑓 0.000046 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000043 ( 0 hom. )
Consequence
POMGNT2
NM_032806.6 missense
NM_032806.6 missense
Scores
4
5
9
Clinical Significance
Conservation
PhyloP100: 7.89
Genes affected
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 2 ACMG points.
PM1
?
In a hotspot region, there are 4 aminoacids with missense pathogenic changes in the window of +-8 aminoacids around while only 2 benign, 2 uncertain in NM_032806.6
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (MetaRNN=0.31501165).
BS1
?
Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.000046 (7/152248) while in subpopulation EAS AF= 0.000777 (4/5148). AF 95% confidence interval is 0.000265. There are 0 homozygotes in gnomad4. There are 2 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
POMGNT2 | NM_032806.6 | c.484G>A | p.Asp162Asn | missense_variant | 2/2 | ENST00000344697.3 | |
POMGNT2 | XM_005265515.4 | c.484G>A | p.Asp162Asn | missense_variant | 3/3 | ||
POMGNT2 | XM_011534163.3 | c.484G>A | p.Asp162Asn | missense_variant | 3/3 | ||
POMGNT2 | XM_017007353.2 | c.484G>A | p.Asp162Asn | missense_variant | 4/4 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
POMGNT2 | ENST00000344697.3 | c.484G>A | p.Asp162Asn | missense_variant | 2/2 | 1 | NM_032806.6 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000526 AC: 8AN: 152130Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.0000796 AC: 20AN: 251374Hom.: 0 AF XY: 0.0000883 AC XY: 12AN XY: 135866
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GnomAD4 exome AF: 0.0000431 AC: 63AN: 1461860Hom.: 0 Cov.: 37 AF XY: 0.0000495 AC XY: 36AN XY: 727230
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GnomAD4 genome ? AF: 0.0000460 AC: 7AN: 152248Hom.: 0 Cov.: 33 AF XY: 0.0000269 AC XY: 2AN XY: 74428
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type a, 8 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Oct 03, 2023 | This sequence change replaces aspartic acid, which is acidic and polar, with asparagine, which is neutral and polar, at codon 162 of the POMGNT2 protein (p.Asp162Asn). This variant is present in population databases (rs201407522, gnomAD 0.06%). This variant has not been reported in the literature in individuals affected with POMGNT2-related conditions. ClinVar contains an entry for this variant (Variation ID: 540493). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt POMGNT2 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. - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Jun 30, 2020 | In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Uncertain
DANN
Uncertain
DEOGEN2
Benign
T;T
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Pathogenic
D
M_CAP
Benign
D
MetaRNN
Benign
T;T
MetaSVM
Uncertain
D
MutationAssessor
Benign
L;L
MutationTaster
Benign
D;D
PrimateAI
Pathogenic
D
PROVEAN
Benign
N;N
REVEL
Uncertain
Sift
Uncertain
D;D
Sift4G
Uncertain
T;T
Polyphen
D;D
Vest4
MVP
MPC
0.64
ClinPred
T
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