rs2657879

Variant names:

• chr12-56471554-A-C
• rs2657879
• NM_013267.4:c.1742T>G

Your query was ambiguous. Multiple possible variants found:

• chr12-56471554-A-C
• chr12-56471554-A-G
• chr12-56471554-A-T

Variant summary

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

The NM_013267.4(GLS2):​c.1742T>G​(p.Leu581Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/22 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. L581F) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: GLS2 NM_013267.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.14
• Publications: 0 publications found

Genes affected

GLS2 (HGNC:29570): (glutaminase 2) The protein encoded by this gene is a mitochondrial phosphate-activated glutaminase that catalyzes the hydrolysis of glutamine to stoichiometric amounts of glutamate and ammonia. Originally thought to be liver-specific, this protein has been found in other tissues as well. Alternative splicing results in multiple transcript variants that encode different isoforms. [provided by RefSeq, Jul 2013]

SPRYD4 (HGNC:27468): (SPRY domain containing 4) Located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000285528 (HGNC:):

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=0.12226939).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_013267.4. 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
	GLS2	NM_013267.4	MANE Select	c.1742T>G	p.Leu581Arg	missense	Exon 18 of 18	NP_037399.2
	SPRYD4	NM_207344.4	MANE Select	c.*1977A>C		3_prime_UTR	Exon 2 of 2	NP_997227.1	Q8WW59
	GLS2	NM_001280797.2		c.947T>G	p.Leu316Arg	missense	Exon 17 of 17	NP_001267726.1	A0A087X004

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GLS2	ENST00000311966.9	TSL:1 MANE Select	c.1742T>G	p.Leu581Arg	missense	Exon 18 of 18	ENSP00000310447.4	Q9UI32-1
	SPRYD4	ENST00000338146.7	TSL:1 MANE Select	c.*1977A>C		3_prime_UTR	Exon 2 of 2	ENSP00000338034.5	Q8WW59
	GLS2	ENST00000390288.6	TSL:1	n.790T>G		non_coding_transcript_exon	Exon 2 of 2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.068
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.50
CADD	Benign	14
DANN	Benign	0.66
DEOGEN2	Benign	0.13	T
Eigen	Benign	-0.59
Eigen_PC	Benign	-0.53
FATHMM_MKL	Benign	0.38	N
LIST_S2	Benign	0.79	T
M_CAP	Benign	0.0072	T
MetaRNN	Benign	0.12	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.4	L
PhyloP100		1.1
PrimateAI	Benign	0.33	T
PROVEAN	Benign	0.21	N
REVEL	Benign	0.035
Sift	Benign	0.53	T
Sift4G	Benign	0.53	T
Polyphen		0.0	B
Vest4		0.27
MutPred		0.38		Loss of stability (P = 0.0358)
MVP		0.38
MPC		0.80
ClinPred		0.075	T
GERP RS		3.1
Varity_R		0.056
gMVP		0.59
Mutation Taster		=98/2	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: rs2657879; hg19: chr12-56865338;