chr2-190880872-C-CGCAGCAGCA

Position:

• chr2-190880872-C-CGCAGCAGCA

Variant summary

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

The NM_014905.5(GLS):​c.-173_-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 0.020 (29 hom., cov: 0)
  • Exomes 𝑓: 0.032 (1483 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-CGCAGCAGCA is Benign according to our data. Variant chr2-190880872-C-CGCAGCAGCA is described in ClinVar as [Likely_benign]. Clinvar id is 3047419.Status of the report is no_assertion_criteria_provided, 0 stars.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0198 (2958/149588) while in subpopulation NFE AF= 0.024 (1614/67242). AF 95% confidence interval is 0.023. There are 29 homozygotes in gnomad4. There are 1406 alleles in male gnomad4 subpopulation. Median coverage is 0. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 29 AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GLS	NM_014905.5	c.-173_-165dup		5_prime_UTR_variant	1/18	ENST00000320717.8
LOC124906110	XR_007087791.1	n.772_773insTGCTGCTGC		non_coding_transcript_exon_variant	2/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GLS	ENST00000320717.8	c.-173_-165dup		5_prime_UTR_variant	1/18	1	NM_014905.5	P1
GLS	ENST00000338435.9	c.-173_-165dup		5_prime_UTR_variant	1/15	1
	ENST00000413911.1	n.843_844insTGCTGCTGC		non_coding_transcript_exon_variant	2/2	3
GLS	ENST00000479552.1	n.41_49dup		non_coding_transcript_exon_variant	1/2	1

Frequencies

GnomAD3 genomes AF: 0.0198 AC: 2958 AN: 149488 Hom.: 29 Cov.: 0

Gnomad AFR AF: 0.0150

Gnomad AMI AF: 0.00554

Gnomad AMR AF: 0.0199

Gnomad ASJ AF: 0.0238

Gnomad EAS AF: 0.00583

Gnomad SAS AF: 0.0169

Gnomad FIN AF: 0.0195

Gnomad MID AF: 0.0159

Gnomad NFE AF: 0.0240

Gnomad OTH AF: 0.0181

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0320 AC: 18963 AN: 592278 Hom.: 1483 Cov.: 0 AF XY: 0.0308 AC XY: 9724 AN XY: 315532

Gnomad4 AFR exome AF: 0.0235

Gnomad4 AMR exome AF: 0.0178

Gnomad4 ASJ exome AF: 0.0282

Gnomad4 EAS exome AF: 0.00416

Gnomad4 SAS exome AF: 0.0196

Gnomad4 FIN exome AF: 0.0218

Gnomad4 NFE exome AF: 0.0388

Gnomad4 OTH exome AF: 0.0307

GnomAD4 genome AF: 0.0198 AC: 2958 AN: 149588 Hom.: 29 Cov.: 0 AF XY: 0.0193 AC XY: 1406 AN XY: 72916

Gnomad4 AFR AF: 0.0149

Gnomad4 AMR AF: 0.0199

Gnomad4 ASJ AF: 0.0238

Gnomad4 EAS AF: 0.00585

Gnomad4 SAS AF: 0.0167

Gnomad4 FIN AF: 0.0195

Gnomad4 NFE AF: 0.0240

Gnomad4 OTH AF: 0.0184

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

May 13, 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;