2-26183092-G-C

Variant names:

• chr2-26183092-G-C
• rs750630201
• NM_001168241.2:c.379G>C

Variant summary

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

The NM_001168241.2(GAREM2):​c.379G>C​(p.Val127Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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. V127I) 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: 7.66
• Publications: 6 publications found

Genes affected

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

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GAREM2	NM_001168241.2	c.379G>C	p.Val127Leu	missense_variant	Exon 3 of 6	ENST00000401533.7	NP_001161713.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GAREM2	ENST00000401533.7	c.379G>C	p.Val127Leu	missense_variant	Exon 3 of 6	1	NM_001168241.2	ENSP00000384593.1
GAREM2	ENST00000407684.1	c.148G>C	p.Val50Leu	missense_variant	Exon 2 of 6	2		ENSP00000384581.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000113

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.90
BayesDel_addAF	Benign	-0.049	T
BayesDel_noAF	Benign	-0.31
CADD	Pathogenic	28
DANN	Uncertain	1.0
DEOGEN2	Benign	0.085	T;.
Eigen	Pathogenic	0.68
Eigen_PC	Pathogenic	0.69
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.97	D;D
M_CAP	Benign	0.013	T
MetaRNN	Uncertain	0.44	T;T
MetaSVM	Benign	-1.1	T
PhyloP100		7.7
PrimateAI	Pathogenic	0.86	D
PROVEAN	Benign	-2.3	N;N
REVEL	Benign	0.14
Sift	Uncertain	0.020	D;D
Sift4G	Uncertain	0.012	D;D
Polyphen		0.66	P;.
Vest4		0.58
MutPred		0.40		Loss of sheet (P = 0.0357);.;
MVP		0.29
ClinPred		0.98	D
GERP RS		5.5
Varity_R		0.34
gMVP		0.71
Mutation Taster		=25/75	disease causing

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: rs750630201; hg19: chr2-26405961;