NM_001168241.2:c.560T>G

Variant names:

• chr2-26184408-T-G
• NM_001168241.2:c.560T>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001168241.2(GAREM2):​c.560T>G​(p.Val187Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000749 in 1,335,800 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 7.5e-7 (0 hom.)
• Consequence: GAREM2 NM_001168241.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.823
• Publications: 0 publications found

Genes affected

GAREM2 (HGNC:27172): (GRB2 associated regulator of MAPK1 subtype 2)

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.1681292).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001168241.2. 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
	GAREM2	NM_001168241.2	MANE Select	c.560T>G	p.Val187Gly	missense	Exon 4 of 6	NP_001161713.1	Q75VX8-1
	GAREM2	NM_001191033.2		c.329T>G	p.Val110Gly	missense	Exon 3 of 6	NP_001177962.1	Q75VX8-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GAREM2	ENST00000401533.7	TSL:1 MANE Select	c.560T>G	p.Val187Gly	missense	Exon 4 of 6	ENSP00000384593.1	Q75VX8-1
	GAREM2	ENST00000407684.1	TSL:2	c.329T>G	p.Val110Gly	missense	Exon 3 of 6	ENSP00000384581.1	Q75VX8-3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 7.49e-7 AC: 1 AN: 1335800 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 658722

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

African (AFR) AF: 0.00 AC: 0 AN: 26864

American (AMR) AF: 0.00 AC: 0 AN: 27750

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23024

East Asian (EAS) AF: 0.00 AC: 0 AN: 28924

South Asian (SAS) AF: 0.00 AC: 0 AN: 74068

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 46700

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5224

European-Non Finnish (NFE) AF: 9.54e-7 AC: 1 AN: 1048664

Other (OTH) AF: 0.00 AC: 0 AN: 54582

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.078
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.48
CADD	Benign	17
DANN	Benign	0.97
DEOGEN2	Benign	0.011	T
Eigen	Benign	-0.45
Eigen_PC	Benign	-0.31
FATHMM_MKL	Benign	0.44	N
LIST_S2	Benign	0.27	T
M_CAP	Benign	0.025	D
MetaRNN	Benign	0.17	T
MetaSVM	Benign	-0.98	T
PhyloP100		0.82
PrimateAI	Pathogenic	0.79	T
PROVEAN	Uncertain	-2.6	D
REVEL	Benign	0.087
Sift	Benign	0.033	D
Sift4G	Uncertain	0.0020	D
Polyphen		0.0	B
Vest4		0.28
MutPred		0.29		Gain of relative solvent accessibility (P = 0.0023)
MVP		0.43
ClinPred		0.13	T
GERP RS		3.9
Varity_R		0.19
gMVP		0.42
Mutation Taster		=97/3	polymorphism

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

Other links and lift over

hg19: chr2-26407277;