2-69345897-T-C

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -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:10
• Conservation: PhyloP100: 2.45
• Publications: 18 publications found

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]

GFPT1 Gene-Disease associations (from GenCC):

• congenital myasthenic syndrome 12

  Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE Submitted by: Genomics England PanelApp, Labcorp Genetics (formerly Invitae), Ambry Genetics, ClinGen, Illumina
• congenital myasthenic syndromes with glycosylation defect

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -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 VariationId is 129151.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.842 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001244710.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GFPT1	NM_001244710.2	MANE Select	c.1105+7A>G		splice_region intron	N/A	NP_001231639.1	Q06210-1
	GFPT1	NM_002056.4		c.1051+7A>G		splice_region intron	N/A	NP_002047.2	Q06210-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GFPT1	ENST00000357308.9	TSL:5 MANE Select	c.1105+7A>G		splice_region intron	N/A	ENSP00000349860.4	Q06210-1
	GFPT1	ENST00000361060.5	TSL:1	c.1051+7A>G		splice_region intron	N/A	ENSP00000354347.4	Q06210-2
	GFPT1	ENST00000955842.1		c.1153+7A>G		splice_region intron	N/A	ENSP00000625901.1

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

GnomAD2 exomes AF: 0.587 AC: 147155 AN: 250732 AF XY: 0.587

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 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

African (AFR) AF: 0.850 AC: 24036 AN: 28284

American (AMR) AF: 0.505 AC: 22394 AN: 44374

Ashkenazi Jewish (ASJ) AF: 0.669 AC: 16469 AN: 24602

East Asian (EAS) AF: 0.455 AC: 17566 AN: 38590

South Asian (SAS) AF: 0.608 AC: 49296 AN: 81068

European-Finnish (FIN) AF: 0.555 AC: 29573 AN: 53320

Middle Eastern (MID) AF: 0.574 AC: 3046 AN: 5310

European-Non Finnish (NFE) AF: 0.574 AC: 507178 AN: 884304

Other (OTH) AF: 0.591 AC: 30779 AN: 52046

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

African (AFR) AF: 0.849 AC: 35279 AN: 41534

American (AMR) AF: 0.566 AC: 8645 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.646 AC: 2239 AN: 3468

East Asian (EAS) AF: 0.469 AC: 2421 AN: 5164

South Asian (SAS) AF: 0.620 AC: 2990 AN: 4822

European-Finnish (FIN) AF: 0.556 AC: 5868 AN: 10554

Middle Eastern (MID) AF: 0.599 AC: 176 AN: 294

European-Non Finnish (NFE) AF: 0.583 AC: 39590 AN: 67964

Other (OTH) AF: 0.631 AC: 1331 AN: 2110

Alfa AF: 0.611 Hom.: 88084

Bravo AF: 0.659

Asia WGS AF: 0.588 AC: 2047 AN: 3478

EpiCase AF: 0.583

EpiControl AF: 0.587

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	6	not specified (6)
-	-	3	Congenital myasthenic syndrome 12 (3)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.69
CADD	Benign	9.3
DANN	Benign	0.89
PhyloP100		2.4
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs6722492; hg19: chr2-69573029; COSMIC: COSV61947668; COSMIC: COSV61947668;