chr2-69387029-A-G

Variant names:

• chr2-69387029-A-G
• rs6720415
• NM_001244710.2:c.7+36T>C

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.7+36T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.594 in 1,484,594 control chromosomes in the GnomAD database, including 266,085 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.66 (34472 hom., cov: 34)
  • Exomes 𝑓: 0.59 (231613 hom.)
• Consequence: GFPT1 NM_001244710.2 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: 0.280

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=-0.54).
• BP6: Variant 2-69387029-A-G is Benign according to our data. Variant chr2-69387029-A-G is described in ClinVar as [Benign]. Clinvar id is 258544.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-69387029-A-G is described in Lovd as [Benign]. Variant chr2-69387029-A-G is described in Lovd as [Likely_pathogenic].
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.862 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GFPT1	NM_001244710.2	c.7+36T>C		intron_variant	Intron 1 of 19	ENST00000357308.9	NP_001231639.1
GFPT1	NM_002056.4	c.7+36T>C		intron_variant	Intron 1 of 18		NP_002047.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GFPT1	ENST00000357308.9	c.7+36T>C		intron_variant	Intron 1 of 19	5	NM_001244710.2	ENSP00000349860.4

Frequencies

GnomAD3 genomes AF: 0.659 AC: 100169 AN: 151978 Hom.: 34431 Cov.: 34

Gnomad AFR AF: 0.869

Gnomad AMI AF: 0.665

Gnomad AMR AF: 0.571

Gnomad ASJ AF: 0.636

Gnomad EAS AF: 0.468

Gnomad SAS AF: 0.622

Gnomad FIN AF: 0.577

Gnomad MID AF: 0.631

Gnomad NFE AF: 0.583

Gnomad OTH AF: 0.628

GnomAD3 exomes AF: 0.574 AC: 74642 AN: 129932 Hom.: 21967 AF XY: 0.577 AC XY: 41255 AN XY: 71456

Gnomad AFR exome AF: 0.858

Gnomad AMR exome AF: 0.501

Gnomad ASJ exome AF: 0.666

Gnomad EAS exome AF: 0.455

Gnomad SAS exome AF: 0.608

Gnomad FIN exome AF: 0.580

Gnomad NFE exome AF: 0.575

Gnomad OTH exome AF: 0.582

GnomAD4 exome AF: 0.587 AC: 781747 AN: 1332502 Hom.: 231613 Cov.: 24 AF XY: 0.587 AC XY: 387819 AN XY: 660692

Gnomad4 AFR exome AF: 0.876

Gnomad4 AMR exome AF: 0.510

Gnomad4 ASJ exome AF: 0.664

Gnomad4 EAS exome AF: 0.454

Gnomad4 SAS exome AF: 0.609

Gnomad4 FIN exome AF: 0.573

Gnomad4 NFE exome AF: 0.582

Gnomad4 OTH exome AF: 0.599

GnomAD4 genome AF: 0.659 AC: 100262 AN: 152092 Hom.: 34472 Cov.: 34 AF XY: 0.655 AC XY: 48699 AN XY: 74342

Gnomad4 AFR AF: 0.869

Gnomad4 AMR AF: 0.570

Gnomad4 ASJ AF: 0.636

Gnomad4 EAS AF: 0.469

Gnomad4 SAS AF: 0.620

Gnomad4 FIN AF: 0.577

Gnomad4 NFE AF: 0.583

Gnomad4 OTH AF: 0.633

Alfa AF: 0.549 Hom.: 2991

Bravo AF: 0.666

Asia WGS AF: 0.593 AC: 2061 AN: 3472

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Jun 16, 2018

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. -

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Congenital myasthenic syndrome 12 Benign:2

Aug 10, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jan 20, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not specified Benign:1

-

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.54
CADD	Benign	14
DANN	Benign	0.73
RBP_binding_hub_radar		1.0
RBP_regulation_power_radar		2.3

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: rs6720415; hg19: chr2-69614161; COSMIC: COSV61951263;