Genetic Variant NM_001286820.2:c.643C>A (chr4-190025758-G-T) – ACMG Classification: Likely_benign (-5 pts)

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4_StrongBP7

The NM_001286820.2(FRG2):c.643C>A(p.Arg215Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0000067 ( 0 hom., cov: 22)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

FRG2
NM_001286820.2 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.869

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:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -5 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-1.0).

BP7

Synonymous conserved (PhyloP=0.869 with no splicing effect.

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.643C>A	p.Arg215Arg	synonymous	Exon 4 of 4	NP_001273749.1	Q64ET8-2
	FRG2	NM_001005217.4		c.640C>A	p.Arg214Arg	synonymous	Exon 4 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.643C>A	p.Arg215Arg	synonymous	Exon 4 of 4	ENSP00000424015.1	Q64ET8-2
FRG2	ENST00000378763.1	TSL:1	c.640C>A	p.Arg214Arg	synonymous	Exon 4 of 4	ENSP00000368039.1	Q64ET8-1
ENSG00000297175	ENST00000745955.1		n.270-2237G>T		intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.00000673

AC:

AN:

148496

Hom.:

Cov.:

show subpopulations

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:

0.0000149

Gnomad OTH

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00000205

AC:

AN:

1459988

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

726056

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.00

AC:

AN:

33454

American (AMR)

AF:

0.00

AC:

AN:

44664

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26094

East Asian (EAS)

AF:

0.00

AC:

AN:

39686

South Asian (SAS)

AF:

0.00

AC:

AN:

86120

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53282

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5750

European-Non Finnish (NFE)

AF:

0.00000270

AC:

AN:

1110644

Other (OTH)

AF:

0.00

AC:

AN:

60294

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.00131091), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.392

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: AS_VQSR

AF:

0.00000673

AC:

AN:

148496

Hom.:

Cov.:

AF XY:

0.0000139

AC XY:

AN XY:

72176

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

40320

American (AMR)

AF:

0.00

AC:

AN:

14780

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3438

East Asian (EAS)

AF:

0.00

AC:

AN:

4894

South Asian (SAS)

AF:

0.00

AC:

AN:

4592

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10258

Middle Eastern (MID)

AF:

0.00

AC:

AN:

302

European-Non Finnish (NFE)

AF:

0.0000149

AC:

AN:

67018

Other (OTH)

AF:

0.00

AC:

AN:

1994

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.725

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-1.0

CADD

Benign

2.8

(source)

DANN

Benign

0.41

PhyloP100

0.87

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

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