chr2-69345897-T-C

Variant names:

• chr2-69345897-T-C
• rs6722492
• NM_001244710.2:c.1105+7A>G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001244710.2(GFPT1):​c.1105+7A>G variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.586 in 1,363,988 control chromosomes in the GnomAD database, including 238,445 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.65 (33607 hom., cov: 32)
  • Exomes 𝑓: 0.58 (204838 hom.)
• Consequence: GFPT1 NM_001244710.2 splice_region, intron
• Scores: Splicing: ADA: 0.004978
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:9
• Conservation: PhyloP100: 2.45

Genes affected

GFPT1 (HGNC:4241): (glutamine--fructose-6-phosphate transaminase 1) This gene encodes the first and rate-limiting enzyme of the hexosamine pathway and controls the flux of glucose into the hexosamine pathway. The product of this gene catalyzes the formation of glucosamine 6-phosphate. [provided by RefSeq, Sep 2008]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.69).
• BP6: Variant 2-69345897-T-C is Benign according to our data. Variant chr2-69345897-T-C is described in ClinVar as [Benign]. Clinvar id is 129151.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-69345897-T-C is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.842 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GFPT1	NM_001244710.2	c.1105+7A>G		splice_region_variant, intron_variant	Intron 12 of 19	ENST00000357308.9	NP_001231639.1
GFPT1	NM_002056.4	c.1051+7A>G		splice_region_variant, intron_variant	Intron 11 of 18		NP_002047.2
GFPT1	XM_017003801.2	c.1180+7A>G		splice_region_variant, intron_variant	Intron 12 of 19		XP_016859290.1
GFPT1	XM_017003802.3	c.1126+7A>G		splice_region_variant, intron_variant	Intron 11 of 18		XP_016859291.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GFPT1	ENST00000357308.9	c.1105+7A>G		splice_region_variant, intron_variant	Intron 12 of 19	5	NM_001244710.2	ENSP00000349860.4
GFPT1	ENST00000361060.5	c.1051+7A>G		splice_region_variant, intron_variant	Intron 11 of 18	1		ENSP00000354347.4
GFPT1	ENST00000674507.1	c.1051+7A>G		splice_region_variant, intron_variant	Intron 11 of 17			ENSP00000501332.1
GFPT1	ENST00000674438.1	c.835+7A>G		splice_region_variant, intron_variant	Intron 9 of 16			ENSP00000501469.1

Frequencies

GnomAD3 genomes AF: 0.652 AC: 99056 AN: 151972 Hom.: 33568 Cov.: 32

Gnomad AFR AF: 0.850

Gnomad AMI AF: 0.667

Gnomad AMR AF: 0.566

Gnomad ASJ AF: 0.646

Gnomad EAS AF: 0.468

Gnomad SAS AF: 0.622

Gnomad FIN AF: 0.556

Gnomad MID AF: 0.604

Gnomad NFE AF: 0.582

Gnomad OTH AF: 0.625

GnomAD3 exomes AF: 0.587 AC: 147155 AN: 250732 Hom.: 44288 AF XY: 0.587 AC XY: 79479 AN XY: 135514

Gnomad AFR exome AF: 0.856

Gnomad AMR exome AF: 0.497

Gnomad ASJ exome AF: 0.675

Gnomad EAS exome AF: 0.469

Gnomad SAS exome AF: 0.615

Gnomad FIN exome AF: 0.559

Gnomad NFE exome AF: 0.585

Gnomad OTH exome AF: 0.581

GnomAD4 exome AF: 0.578 AC: 700337 AN: 1211898 Hom.: 204838 Cov.: 17 AF XY: 0.579 AC XY: 356520 AN XY: 615540

Gnomad4 AFR exome AF: 0.850

Gnomad4 AMR exome AF: 0.505

Gnomad4 ASJ exome AF: 0.669

Gnomad4 EAS exome AF: 0.455

Gnomad4 SAS exome AF: 0.608

Gnomad4 FIN exome AF: 0.555

Gnomad4 NFE exome AF: 0.574

Gnomad4 OTH exome AF: 0.591

GnomAD4 genome AF: 0.652 AC: 99147 AN: 152090 Hom.: 33607 Cov.: 32 AF XY: 0.647 AC XY: 48113 AN XY: 74346

Gnomad4 AFR AF: 0.849

Gnomad4 AMR AF: 0.566

Gnomad4 ASJ AF: 0.646

Gnomad4 EAS AF: 0.469

Gnomad4 SAS AF: 0.620

Gnomad4 FIN AF: 0.556

Gnomad4 NFE AF: 0.583

Gnomad4 OTH AF: 0.631

Alfa AF: 0.597 Hom.: 54660

Bravo AF: 0.659

Asia WGS AF: 0.588 AC: 2047 AN: 3478

EpiCase AF: 0.583

EpiControl AF: 0.587

ClinVar

Significance: Benign

Submissions summary: Benign:9

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:5

-

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Feb 04, 2016

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Apr 29, 2021

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Aug 15, 2013

Genetic Services Laboratory, University of Chicago

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jun 12, 2014

Eurofins Ntd Llc (ga)

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Congenital myasthenic syndrome 12 Benign:3

Aug 10, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

not provided Benign:1

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.69
CADD	Benign	9.3
DANN	Benign	0.89

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.0050
dbscSNV1_RF	Benign	0.13
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: rs6722492; hg19: chr2-69573029; COSMIC: COSV61947668; COSMIC: COSV61947668;