10-48184809-C-G
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_001018071.4(FRMPD2):c.2432G>C(p.Gly811Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000223 in 1,613,694 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.00016 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000075 ( 0 hom. )
Consequence
FRMPD2
NM_001018071.4 missense
NM_001018071.4 missense
Scores
2
5
7
Clinical Significance
Conservation
PhyloP100: 2.61
Genes affected
FRMPD2 (HGNC:28572): (FERM and PDZ domain containing 2) This gene encodes a peripheral membrane protein and is located in a region of chromosome 10q that contains a segmental duplication. This copy of the gene is full-length and is in the telomeric duplicated region. Two other more centromerically proximal copies of the gene are partial and may represent pseudogenes. This full-length gene appears to function in the establishment and maintenance of cell polarization. The protein is recruited to cell-cell junctions in an E-cadherin-dependent manner, and is selectively localized at the basolateral membrane in polarized epithelial cells. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2009]
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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 |
---|---|---|---|---|---|---|---|
FRMPD2 | NM_001018071.4 | c.2432G>C | p.Gly811Ala | missense_variant | 19/29 | ENST00000374201.8 | |
FRMPD2 | NM_001318191.1 | c.2357G>C | p.Gly786Ala | missense_variant | 17/27 | ||
FRMPD2 | XM_047424652.1 | c.2429G>C | p.Gly810Ala | missense_variant | 19/22 | ||
FRMPD2 | XM_047424653.1 | c.2339G>C | p.Gly780Ala | missense_variant | 17/20 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
FRMPD2 | ENST00000374201.8 | c.2432G>C | p.Gly811Ala | missense_variant | 19/29 | 1 | NM_001018071.4 | P2 |
Frequencies
GnomAD3 genomes ? AF: 0.000164 AC: 25AN: 152176Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000199 AC: 5AN: 250838Hom.: 0 AF XY: 0.0000295 AC XY: 4AN XY: 135564
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GnomAD4 exome AF: 0.00000753 AC: 11AN: 1461518Hom.: 0 Cov.: 31 AF XY: 0.00000688 AC XY: 5AN XY: 727026
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GnomAD4 genome ? AF: 0.000164 AC: 25AN: 152176Hom.: 0 Cov.: 32 AF XY: 0.000175 AC XY: 13AN XY: 74340
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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 | Feb 10, 2022 | The c.2432G>C (p.G811A) alteration is located in exon 19 (coding exon 19) of the FRMPD2 gene. This alteration results from a G to C substitution at nucleotide position 2432, causing the glycine (G) at amino acid position 811 to be replaced by an alanine (A). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Pathogenic
Dann
Uncertain
DEOGEN2
Benign
T;T;.
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D;D;D
M_CAP
Benign
T
MetaRNN
Uncertain
D;D;D
MetaSVM
Uncertain
T
MutationTaster
Benign
D;D;D
PrimateAI
Benign
T
Polyphen
1.0
.;D;D
Vest4
0.42, 0.44
MVP
0.54
MPC
0.24
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
DS_AG_spliceai
Position offset: -3
Find out detailed SpliceAI scores and Pangolin per-transcript scores at