rs2638315

Variant names:

• chr12-56471272-G-C
• rs2638315
• NM_013267.4:c.*215C>G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_013267.4(GLS2):​c.*215C>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.167 in 533,762 control chromosomes in the GnomAD database, including 8,150 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.15 (2053 hom., cov: 32)
  • Exomes 𝑓: 0.17 (6097 hom.)
• Consequence: GLS2 NM_013267.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.197

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.201 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GLS2	NM_013267.4	c.*215C>G		3_prime_UTR_variant	Exon 18 of 18	ENST00000311966.9	NP_037399.2
SPRYD4	NM_207344.4	c.*1695G>C		3_prime_UTR_variant	Exon 2 of 2	ENST00000338146.7	NP_997227.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GLS2	ENST00000311966	c.*215C>G		3_prime_UTR_variant	Exon 18 of 18	1	NM_013267.4	ENSP00000310447.4
SPRYD4	ENST00000338146.7	c.*1695G>C		3_prime_UTR_variant	Exon 2 of 2	1	NM_207344.4	ENSP00000338034.5
ENSG00000285528	ENST00000648304.1	n.182+16665C>G		intron_variant	Intron 1 of 3			ENSP00000497190.1

Frequencies

GnomAD3 genomes AF: 0.153 AC: 23241 AN: 152102 Hom.: 2046 Cov.: 32

Gnomad AFR AF: 0.0712

Gnomad AMI AF: 0.314

Gnomad AMR AF: 0.206

Gnomad ASJ AF: 0.186

Gnomad EAS AF: 0.0898

Gnomad SAS AF: 0.148

Gnomad FIN AF: 0.186

Gnomad MID AF: 0.222

Gnomad NFE AF: 0.186

Gnomad OTH AF: 0.167

GnomAD4 exome AF: 0.172 AC: 65706 AN: 381544 Hom.: 6097 Cov.: 5 AF XY: 0.173 AC XY: 34040 AN XY: 197316

Gnomad4 AFR exome AF: 0.0707

Gnomad4 AMR exome AF: 0.211

Gnomad4 ASJ exome AF: 0.194

Gnomad4 EAS exome AF: 0.103

Gnomad4 SAS exome AF: 0.138

Gnomad4 FIN exome AF: 0.179

Gnomad4 NFE exome AF: 0.185

Gnomad4 OTH exome AF: 0.168

GnomAD4 genome AF: 0.153 AC: 23260 AN: 152218 Hom.: 2053 Cov.: 32 AF XY: 0.154 AC XY: 11472 AN XY: 74412

Gnomad4 AFR AF: 0.0712

Gnomad4 AMR AF: 0.207

Gnomad4 ASJ AF: 0.186

Gnomad4 EAS AF: 0.0891

Gnomad4 SAS AF: 0.148

Gnomad4 FIN AF: 0.186

Gnomad4 NFE AF: 0.186

Gnomad4 OTH AF: 0.168

Alfa AF: 0.181 Hom.: 1443

Bravo AF: 0.150

Asia WGS AF: 0.141 AC: 492 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.1
DANN	Benign	0.69

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

Publications

LitVar

Other links and lift over

dbSNP: rs2638315; hg19: chr12-56865056;