2-26187535-G-C

Variant names:

• chr2-26187535-G-C
• rs889078345
• NM_001168241.2:c.1903G>C

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001168241.2(GAREM2):​c.1903G>C​(p.Gly635Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000868 in 1,381,996 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000087 (0 hom.)
• Consequence: GAREM2 NM_001168241.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.86
• 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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.3161291).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GAREM2	NM_001168241.2	c.1903G>C	p.Gly635Arg	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.1903G>C	p.Gly635Arg	missense_variant	Exon 6 of 6	1	NM_001168241.2	ENSP00000384593.1
GAREM2	ENST00000407684.1	c.1453-180G>C		intron_variant	Intron 5 of 5	2		ENSP00000384581.1
GAREM2	ENST00000496070.1	n.*77G>C		downstream_gene_variant		3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000868 AC: 12 AN: 1381996 Hom.: 0 Cov.: 32 AF XY: 0.00000587 AC XY: 4 AN XY: 680936

African (AFR) AF: 0.00 AC: 0 AN: 30730

American (AMR) AF: 0.00 AC: 0 AN: 31956

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23972

East Asian (EAS) AF: 0.00 AC: 0 AN: 35572

South Asian (SAS) AF: 0.00 AC: 0 AN: 76490

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 48882

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5574

European-Non Finnish (NFE) AF: 0.0000112 AC: 12 AN: 1071694

Other (OTH) AF: 0.00 AC: 0 AN: 57126

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.38
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.42
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.024	T
Eigen	Uncertain	0.26
Eigen_PC	Uncertain	0.23
FATHMM_MKL	Uncertain	0.85	D
LIST_S2	Benign	0.78	T
M_CAP	Benign	0.016	T
MetaRNN	Benign	0.32	T
MetaSVM	Benign	-1.1	T
PhyloP100		2.9
PrimateAI	Uncertain	0.69	T
PROVEAN	Uncertain	-2.7	D
REVEL	Benign	0.16
Sift	Benign	0.13	T
Sift4G	Benign	0.15	T
Polyphen		1.0	D
Vest4		0.28
MutPred		0.19		Gain of phosphorylation at S634 (P = 0.1217);
MVP		0.46
ClinPred		0.91	D
GERP RS		5.1
Varity_R		0.11
gMVP		0.37
Mutation Taster		=95/5	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs889078345; hg19: chr2-26410404;