chr10-48163550-C-A
Variant names:
Variant summary
Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate
The NM_001018071.4(FRMPD2):c.3659G>T(p.Gly1220Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.0000068 ( 0 hom., cov: 28)
Exomes 𝑓: 0.0000096 ( 0 hom. )
Failed GnomAD Quality Control
Consequence
FRMPD2
NM_001018071.4 missense
NM_001018071.4 missense
Scores
4
15
Clinical Significance
Conservation
PhyloP100: 0.0850
Publications
0 publications found
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]
Genome browser will be placed here
ACMG classification
Classification was made for transcript
Our verdict: Likely_benign. The variant received -2 ACMG points.
BP4
Computational evidence support a benign effect (MetaRNN=0.09897518).
Transcripts
RefSeq
| Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|
| FRMPD2 | NM_001018071.4 | c.3659G>T | p.Gly1220Val | missense_variant | Exon 28 of 29 | ENST00000374201.8 | NP_001018081.4 | |
| FRMPD2 | NM_001318191.1 | c.3584G>T | p.Gly1195Val | missense_variant | Exon 26 of 27 | NP_001305120.1 | ||
| FRMPD2 | NM_001042512.3 | c.692G>T | p.Gly231Val | missense_variant | Exon 5 of 6 | NP_001035977.3 | ||
| FRMPD2 | XM_017015744.2 | c.515G>T | p.Gly172Val | missense_variant | Exon 5 of 6 | XP_016871233.1 |
Ensembl
Frequencies
GnomAD3 genomes 0.00000678 AC: 1AN: 147508Hom.: 0 Cov.: 28 show subpopulations
GnomAD3 genomes
AF:
AC:
1
AN:
147508
Hom.:
Cov.:
28
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: 0.00000965 AC: 10AN: 1036470Hom.: 0 Cov.: 15 AF XY: 0.00000750 AC XY: 4AN XY: 533264 show subpopulations
GnomAD4 exome
Data not reliable, filtered out with message: AS_VQSR
AF:
AC:
10
AN:
1036470
Hom.:
Cov.:
15
AF XY:
AC XY:
4
AN XY:
533264
show subpopulations
African (AFR)
AF:
AC:
0
AN:
24210
American (AMR)
AF:
AC:
0
AN:
44112
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
23238
East Asian (EAS)
AF:
AC:
0
AN:
37542
South Asian (SAS)
AF:
AC:
0
AN:
77334
European-Finnish (FIN)
AF:
AC:
0
AN:
53220
Middle Eastern (MID)
AF:
AC:
0
AN:
3328
European-Non Finnish (NFE)
AF:
AC:
10
AN:
727490
Other (OTH)
AF:
AC:
0
AN:
45996
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.485
Heterozygous variant carriers
0
1
1
2
2
3
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
GnomAD4 genome 0.00000677 AC: 1AN: 147610Hom.: 0 Cov.: 28 AF XY: 0.00 AC XY: 0AN XY: 71988 show subpopulations
GnomAD4 genome
Data not reliable, filtered out with message: AS_VQSR
AF:
AC:
1
AN:
147610
Hom.:
Cov.:
28
AF XY:
AC XY:
0
AN XY:
71988
show subpopulations
African (AFR)
AF:
AC:
0
AN:
39098
American (AMR)
AF:
AC:
0
AN:
14874
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
3424
East Asian (EAS)
AF:
AC:
0
AN:
5028
South Asian (SAS)
AF:
AC:
0
AN:
4632
European-Finnish (FIN)
AF:
AC:
0
AN:
10338
Middle Eastern (MID)
AF:
AC:
0
AN:
290
European-Non Finnish (NFE)
AF:
AC:
1
AN:
67018
Other (OTH)
AF:
AC:
0
AN:
2008
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.425
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Jan 23, 2023
Ambry Genetics
Significance:Uncertain significance
Review Status:criteria provided, single submitter
Collection Method:clinical testing
The c.3659G>T (p.G1220V) alteration is located in exon 28 (coding exon 28) of the FRMPD2 gene. This alteration results from a G to T substitution at nucleotide position 3659, causing the glycine (G) at amino acid position 1220 to be replaced by a valine (V). 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
DANN
Benign
DEOGEN2
Benign
T;T;.
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
N
LIST_S2
Benign
T;T;T
M_CAP
Benign
D
MetaRNN
Benign
T;T;T
MetaSVM
Benign
T
MutationAssessor
Benign
.;L;.
PhyloP100
PrimateAI
Uncertain
T
PROVEAN
Uncertain
.;D;D
REVEL
Benign
Sift
Uncertain
.;D;D
Sift4G
Uncertain
.;D;D
Polyphen
0.18, 0.13
.;B;B
Vest4
0.19, 0.16
MutPred
Gain of stability (P = 0.0727);Gain of stability (P = 0.0727);.;
MVP
0.27
MPC
2.1
ClinPred
T
GERP RS
Varity_R
gMVP
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
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