NM_001286820.2:c.161A>G

Variant names:

• chr4-190027044-T-C
• NM_001286820.2:c.161A>G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001286820.2(FRG2):​c.161A>G​(p.Lys54Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. K54T) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 15)
• Consequence: FRG2 NM_001286820.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.737

Genes affected

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

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.08811894).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FRG2	NM_001286820.2	c.161A>G	p.Lys54Arg	missense_variant	Exon 1 of 4	ENST00000504750.6	NP_001273749.1
FRG2	NM_001005217.4	c.161A>G	p.Lys54Arg	missense_variant	Exon 1 of 4		NP_001005217.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FRG2	ENST00000504750.6	c.161A>G	p.Lys54Arg	missense_variant	Exon 1 of 4	1	NM_001286820.2	ENSP00000424015.1
FRG2	ENST00000378763.1	c.161A>G	p.Lys54Arg	missense_variant	Exon 1 of 4	1		ENSP00000368039.1

Frequencies

GnomAD3 genomes Cov.: 15

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 15

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.30	T
BayesDel_noAF	Benign	-0.66
CADD	Benign	11
DANN	Benign	0.83
DEOGEN2	Benign	0.024	.;T
Eigen	Benign	-0.74
Eigen_PC	Benign	-0.84
FATHMM_MKL	Benign	0.032	N
M_CAP	Benign	0.0016	T
MetaRNN	Benign	0.088	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.6	L;L
PROVEAN	Benign	-1.3	N;N
REVEL	Benign	0.051
Sift	Benign	0.060	T;D
Sift4G	Benign	0.29	T;T
Polyphen		0.59	.;P
Vest4		0.14
MutPred		0.23		Loss of ubiquitination at K54 (P = 6e-04);Loss of ubiquitination at K54 (P = 6e-04);
MVP		0.014
MPC		1.8
ClinPred		0.22	T
GERP RS		0.35
Varity_R		0.044
gMVP		0.0045

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: chr4-190948199;