2-26185167-G-C

Variant names:

• chr2-26185167-G-C
• rs1669202165
• NM_001168241.2:c.1319G>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001168241.2(GAREM2):​c.1319G>C​(p.Gly440Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000738 in 1,354,964 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. G440D) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 7.4e-7 (0 hom.)
• Consequence: GAREM2 NM_001168241.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.12
• Publications: 0 publications found

Genes affected

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

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.046635717).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GAREM2	NM_001168241.2	c.1319G>C	p.Gly440Ala	missense_variant	Exon 4 of 6	ENST00000401533.7	NP_001161713.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GAREM2	ENST00000401533.7	c.1319G>C	p.Gly440Ala	missense_variant	Exon 4 of 6	1	NM_001168241.2	ENSP00000384593.1
GAREM2	ENST00000407684.1	c.1088G>C	p.Gly363Ala	missense_variant	Exon 3 of 6	2		ENSP00000384581.1
GAREM2	ENST00000496070.1	n.-65G>C		upstream_gene_variant		3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 7.38e-7 AC: 1 AN: 1354964 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 668226

African (AFR) AF: 0.00 AC: 0 AN: 27876

American (AMR) AF: 0.00 AC: 0 AN: 33214

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24056

East Asian (EAS) AF: 0.00 AC: 0 AN: 31776

South Asian (SAS) AF: 0.0000130 AC: 1 AN: 77142

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 33162

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4002

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1067256

Other (OTH) AF: 0.00 AC: 0 AN: 56480

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.082
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.54
CADD	Benign	12
DANN	Benign	0.91
DEOGEN2	Benign	0.0035	T;.
Eigen	Benign	-0.86
Eigen_PC	Benign	-0.84
FATHMM_MKL	Benign	0.56	D
LIST_S2	Benign	0.57	T;T
M_CAP	Benign	0.036	D
MetaRNN	Benign	0.047	T;T
MetaSVM	Benign	-0.97	T
PhyloP100		1.1
PrimateAI	Pathogenic	0.85	D
PROVEAN	Benign	-0.69	N;N
REVEL	Benign	0.036
Sift	Benign	0.49	T;T
Sift4G	Benign	0.17	T;T
Polyphen		0.018	B;.
Vest4		0.032
MutPred		0.28		Loss of loop (P = 0.0512);.;
MVP		0.048
ClinPred		0.065	T
GERP RS		2.8
Varity_R		0.069
gMVP		0.26
Mutation Taster		=92/8	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: rs1669202165; hg19: chr2-26408036;