Genetic Variant NM_001286820.2:c.278G>C (chr4-190026440-C-G) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -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. 15/21 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. R93W) has been classified as Uncertain significance.

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

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.398

Publications

0 publications found

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]

FRG2 links:

ENSG00000297175 (HGNC:):

ENSG00000297175 links:

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=0.11275831).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001286820.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FRG2	NM_001286820.2	MANE Select	c.278G>C	p.Arg93Pro	missense	Exon 3 of 4	NP_001273749.1	Q64ET8-2
	FRG2	NM_001005217.4		c.275G>C	p.Arg92Pro	missense	Exon 3 of 4	NP_001005217.1	Q64ET8-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
FRG2	ENST00000504750.6	TSL:1 MANE Select	c.278G>C	p.Arg93Pro	missense	Exon 3 of 4	ENSP00000424015.1	Q64ET8-2
FRG2	ENST00000378763.1	TSL:1	c.275G>C	p.Arg92Pro	missense	Exon 3 of 4	ENSP00000368039.1	Q64ET8-1
ENSG00000297175	ENST00000745955.1		n.270-1555C>G		intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

143008

Hom.:

Cov.:

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:

AN:

1450354

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

721960

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

32392

American (AMR)

AF:

0.00

AC:

AN:

44520

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26072

East Asian (EAS)

AF:

0.00

AC:

AN:

39482

South Asian (SAS)

AF:

0.0000233

AC:

AN:

85716

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53404

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5722

European-Non Finnish (NFE)

AF:

9.07e-7

AC:

AN:

1103096

Other (OTH)

AF:

0.00

AC:

AN:

59950

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Data not reliable, filtered out with message: AC0;AS_VQSR

AF:

0.00

AC:

AN:

143008

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

69492

African (AFR)

AF:

0.00

AC:

AN:

36916

American (AMR)

AF:

0.00

AC:

AN:

14432

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3384

East Asian (EAS)

AF:

0.00

AC:

AN:

4776

South Asian (SAS)

AF:

0.00

AC:

AN:

4406

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10080

Middle Eastern (MID)

AF:

0.00

AC:

AN:

306

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

65884

Other (OTH)

AF:

0.00

AC:

AN:

1920

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.18

BayesDel_addAF

Benign

-0.28

BayesDel_noAF

Benign

-0.65

CADD

Benign

4.5

(source)

DANN

Benign

0.63

DEOGEN2

Benign

0.012

Eigen

Benign

-0.78

Eigen_PC

Benign

-0.90

FATHMM_MKL

Benign

0.024

M_CAP

Benign

0.0024

MetaRNN

Benign

0.11

MetaSVM

Benign

-0.92

MutationAssessor

Benign

0.20

PhyloP100

-0.40

PROVEAN

Benign

-0.73

REVEL

Benign

0.058

Sift

Benign

0.13

Sift4G

Benign

0.29

Polyphen

0.43

Vest4

0.33

MutPred

0.20

Gain of glycosylation at S90 (P = 0.0017)

MVP

0.061

MPC

2.7

ClinPred

0.16

GERP RS

0.35

Varity_R

0.24

gMVP

0.010

Mutation Taster

=97/3

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over