2-190880872-C-CGCAGCAGCAGCAGCAGCAGCA

Position:

• chr2-190880872-C-CGCAGCAGCAGCAGCAGCAGCA

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP6 BS1 BS2

The NM_014905.5(GLS):​c.-185_-165dup variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Likely benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.0021 (2 hom., cov: 0)
  • Exomes 𝑓: 0.0018 (13 hom.)
  • Failed GnomAD Quality Control
• Consequence: GLS NM_014905.5 5_prime_UTR
• Clinical Significance: Likely benign no assertion criteria provided B:1
• Conservation: PhyloP100: -0.922

Genes affected

GLS (HGNC:4331): (glutaminase) This gene encodes the K-type mitochondrial glutaminase. The encoded protein is an phosphate-activated amidohydrolase that catalyzes the hydrolysis of glutamine to glutamate and ammonia. This protein is primarily expressed in the brain and kidney plays an essential role in generating energy for metabolism, synthesizing the brain neurotransmitter glutamate and maintaining acid-base balance in the kidney. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Jan 2012]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -9 ACMG points.

• BP6: Variant 2-190880872-C-CGCAGCAGCAGCAGCAGCAGCA is Benign according to our data. Variant chr2-190880872-C-CGCAGCAGCAGCAGCAGCAGCA is described in ClinVar as [Likely_benign]. Clinvar id is 3054034.Status of the report is no_assertion_criteria_provided, 0 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00213 (318/149606) while in subpopulation AFR AF= 0.00246 (100/40698). AF 95% confidence interval is 0.00207. There are 2 homozygotes in gnomad4. There are 150 alleles in male gnomad4 subpopulation. Median coverage is 0. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 2 AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GLS	NM_014905.5	c.-185_-165dup		5_prime_UTR_variant	1/18	ENST00000320717.8
LOC124906110	XR_007087791.1	n.772_773insTGCTGCTGCTGCTGCTGCTGC		non_coding_transcript_exon_variant	2/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GLS	ENST00000320717.8	c.-185_-165dup		5_prime_UTR_variant	1/18	1	NM_014905.5	P1
GLS	ENST00000338435.9	c.-185_-165dup		5_prime_UTR_variant	1/15	1
	ENST00000413911.1	n.843_844insTGCTGCTGCTGCTGCTGCTGC		non_coding_transcript_exon_variant	2/2	3
GLS	ENST00000479552.1	n.29_49dup		non_coding_transcript_exon_variant	1/2	1

Frequencies

GnomAD3 genomes AF: 0.00212 AC: 317 AN: 149506 Hom.: 2 Cov.: 0

Gnomad AFR AF: 0.00244

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00166

Gnomad ASJ AF: 0.00261

Gnomad EAS AF: 0.00181

Gnomad SAS AF: 0.00235

Gnomad FIN AF: 0.000392

Gnomad MID AF: 0.00318

Gnomad NFE AF: 0.00226

Gnomad OTH AF: 0.00342

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00182 AC: 1080 AN: 593470 Hom.: 13 Cov.: 0 AF XY: 0.00176 AC XY: 558 AN XY: 316202

Gnomad4 AFR exome AF: 0.00277

Gnomad4 AMR exome AF: 0.00125

Gnomad4 ASJ exome AF: 0.00341

Gnomad4 EAS exome AF: 0.000976

Gnomad4 SAS exome AF: 0.00166

Gnomad4 FIN exome AF: 0.000414

Gnomad4 NFE exome AF: 0.00194

Gnomad4 OTH exome AF: 0.00198

GnomAD4 genome AF: 0.00213 AC: 318 AN: 149606 Hom.: 2 Cov.: 0 AF XY: 0.00206 AC XY: 150 AN XY: 72924

Gnomad4 AFR AF: 0.00246

Gnomad4 AMR AF: 0.00165

Gnomad4 ASJ AF: 0.00261

Gnomad4 EAS AF: 0.00181

Gnomad4 SAS AF: 0.00235

Gnomad4 FIN AF: 0.000392

Gnomad4 NFE AF: 0.00226

Gnomad4 OTH AF: 0.00338

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

Submissions by phenotype

GLS-related disorder Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Nov 01, 2021

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs57674096; hg19: chr2-191745598;