3-170997894-GTT-GTTTTT

Variant names:

• chr3-170997894-G-GTTT
• rs573575421
• NM_000340.2:c.*6_*8dupAAA

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_000340.2(SLC2A2):​c.*6_*8dupAAA variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000778 in 1,284,944 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.8e-7 (0 hom.)
• Consequence: SLC2A2 NM_000340.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.929
• Publications: 0 publications found

Genes affected

SLC2A2 (HGNC:11006): (solute carrier family 2 member 2) This gene encodes an integral plasma membrane glycoprotein of the liver, islet beta cells, intestine, and kidney epithelium. The encoded protein mediates facilitated bidirectional glucose transport. Because of its low affinity for glucose, it has been suggested as a glucose sensor. Mutations in this gene are associated with susceptibility to diseases, including Fanconi-Bickel syndrome and noninsulin-dependent diabetes mellitus (NIDDM). Alternative splicing results in multiple transcript variants of this gene. [provided by RefSeq, Jul 2013]

SLC2A2 Gene-Disease associations (from GenCC):

• glycogen storage disease due to GLUT2 deficiency

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: PanelApp Australia, Orphanet, G2P, Labcorp Genetics (formerly Invitae), Genomics England PanelApp
• neonatal diabetes mellitus

  Inheritance: AR Classification: STRONG Submitted by: Genomics England PanelApp
• permanent neonatal diabetes mellitus

  Inheritance: AR Classification: STRONG Submitted by: Genomics England PanelApp
• transient neonatal diabetes mellitus

  Inheritance: AR Classification: STRONG Submitted by: Genomics England PanelApp

ENSG00000286856 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000340.2. 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
	SLC2A2	NM_000340.2	MANE Select	c.*6_*8dupAAA		3_prime_UTR	Exon 11 of 11	NP_000331.1	P11168-1
	SLC2A2	NM_001278658.2		c.*6_*8dupAAA		3_prime_UTR	Exon 10 of 10	NP_001265587.1	P11168-2
	SLC2A2	NM_001278659.2		c.*6_*8dupAAA		3_prime_UTR	Exon 10 of 10	NP_001265588.1	Q6PAU8

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC2A2	ENST00000314251.8	TSL:1 MANE Select	c.*6_*8dupAAA		3_prime_UTR	Exon 11 of 11	ENSP00000323568.3	P11168-1
	SLC2A2	ENST00000497642.5	TSL:1	n.*1048_*1050dupAAA		non_coding_transcript_exon	Exon 10 of 10	ENSP00000418456.1	A0A0C4DH64
	SLC2A2	ENST00000497642.5	TSL:1	n.*1048_*1050dupAAA		3_prime_UTR	Exon 10 of 10	ENSP00000418456.1	A0A0C4DH64

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.78e-7 AC: 1 AN: 1284944 Hom.: 0 Cov.: 30 AF XY: 0.00000156 AC XY: 1 AN XY: 639828

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 29406

American (AMR) AF: 0.00 AC: 0 AN: 39818

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 22890

East Asian (EAS) AF: 0.00 AC: 0 AN: 35324

South Asian (SAS) AF: 0.0000133 AC: 1 AN: 75372

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 47526

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5244

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 976242

Other (OTH) AF: 0.00 AC: 0 AN: 53122

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.93

Splicing

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

Other links and lift over

dbSNP: rs573575421; hg19: chr3-170715683;