4-190026440-C-G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001286820.2(FRG2):​c.278G>C​(p.Arg93Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R93Q) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.0 ( 0 hom., cov: 22)
Exomes 𝑓: 0.0000021 ( 1 hom. )
Failed GnomAD Quality Control

Consequence

FRG2
NM_001286820.2 missense

Scores

17

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.398
Variant links:
Genes affected
FRG2 (HGNC:19136): (FSHD region gene 2) Predicted to be located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.11275831).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
FRG2NM_001286820.2 linkc.278G>C p.Arg93Pro missense_variant Exon 3 of 4 ENST00000504750.6 NP_001273749.1 Q64ET8-2
FRG2NM_001005217.4 linkc.275G>C p.Arg92Pro missense_variant Exon 3 of 4 NP_001005217.1 Q64ET8-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
FRG2ENST00000504750.6 linkc.278G>C p.Arg93Pro missense_variant Exon 3 of 4 1 NM_001286820.2 ENSP00000424015.1 Q64ET8-2
FRG2ENST00000378763.1 linkc.275G>C p.Arg92Pro missense_variant Exon 3 of 4 1 ENSP00000368039.1 Q64ET8-1

Frequencies

GnomAD3 genomes
AF:
0.00
AC:
0
AN:
143008
Hom.:
0
Cov.:
22
FAILED QC
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD4 exome
Data not reliable, filtered out with message: AS_VQSR
AF:
0.00000207
AC:
3
AN:
1450354
Hom.:
1
Cov.:
30
AF XY:
0.00
AC XY:
0
AN XY:
721960
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000233
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
9.07e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Data not reliable, filtered out with message: AC0;AS_VQSR
AF:
0.00
AC:
0
AN:
143008
Hom.:
0
Cov.:
22
AF XY:
0.00
AC XY:
0
AN XY:
69492
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Sep 11, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.275G>C (p.R92P) alteration is located in exon 3 (coding exon 3) of the FRG2 gene. This alteration results from a G to C substitution at nucleotide position 275, causing the arginine (R) at amino acid position 92 to be replaced by a proline (P). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.18
BayesDel_addAF
Benign
-0.28
T
BayesDel_noAF
Benign
-0.65
CADD
Benign
4.5
DANN
Benign
0.63
DEOGEN2
Benign
0.012
.;T
Eigen
Benign
-0.78
Eigen_PC
Benign
-0.90
FATHMM_MKL
Benign
0.024
N
M_CAP
Benign
0.0024
T
MetaRNN
Benign
0.11
T;T
MetaSVM
Benign
-0.92
T
MutationAssessor
Benign
0.20
.;N
PROVEAN
Benign
-0.73
N;N
REVEL
Benign
0.058
Sift
Benign
0.13
T;T
Sift4G
Benign
0.29
T;T
Polyphen
0.43
.;B
Vest4
0.33
MutPred
0.20
.;Gain of glycosylation at S90 (P = 0.0017);
MVP
0.061
MPC
2.7
ClinPred
0.16
T
GERP RS
0.35
Varity_R
0.24
gMVP
0.010

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.030
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr4-190947595; API