NM_001168241.2:c.1754G>T

Variant names:

• chr2-26187386-G-T
• rs956746017
• NM_001168241.2:c.1754G>T

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.1754G>T​(p.Arg585Leu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/21 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. R585Q) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: GAREM2 NM_001168241.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.75
• Publications: 1 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=0.13949612).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GAREM2	NM_001168241.2	c.1754G>T	p.Arg585Leu	missense_variant	Exon 6 of 6	ENST00000401533.7	NP_001161713.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GAREM2	ENST00000401533.7	c.1754G>T	p.Arg585Leu	missense_variant	Exon 6 of 6	1	NM_001168241.2	ENSP00000384593.1
GAREM2	ENST00000496070.1	n.201G>T		non_coding_transcript_exon_variant	Exon 2 of 2	3
GAREM2	ENST00000407684.1	c.1452+71G>T		intron_variant	Intron 5 of 5	2		ENSP00000384581.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.49
CADD	Benign	17
DANN	Benign	0.71
DEOGEN2	Benign	0.039	T
Eigen	Benign	-0.50
Eigen_PC	Benign	-0.41
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Benign	0.76	T
M_CAP	Benign	0.010	T
MetaRNN	Benign	0.14	T
MetaSVM	Benign	-1.0	T
PhyloP100		3.8
PrimateAI	Benign	0.40	T
PROVEAN	Benign	-2.3	N
REVEL	Benign	0.026
Sift	Benign	0.48	T
Sift4G	Benign	0.67	T
Polyphen		0.093	B
Vest4		0.29
MutPred		0.30		Loss of solvent accessibility (P = 0.0079);
MVP		0.38
ClinPred		0.55	D
GERP RS		4.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.21
gMVP		0.28
Mutation Taster		=96/4	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

dbSNP: rs956746017; hg19: chr2-26410255;