dbSNP rs987447860: SLC5A2:p.His525ProfsTer49 (chr16-31489216-T-TCGGCGTGCCCAGCTTTCCTCTG) – ACMG Classification: Pathogenic (10 pts)

Variant summary

Our verdict is Pathogenic. Variant got 10 ACMG points: 10P and 0B. PVS1PP5_Moderate

The NM_003041.4(SLC5A2):c.1552_1573dupCCAGCTTTCCTCTGCGGCGTGC(p.His525ProfsTer49) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000373 in 1,610,198 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely pathogenic (★). Variant results in nonsense mediated mRNA decay.

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

SLC5A2
NM_003041.4 frameshift

Scores

Not classified

Clinical Significance

Likely pathogenic criteria provided, single submitter P:1U:1

Conservation

PhyloP100: 0.119

Variant links:

Genes affected

SLC5A2 (HGNC:11037): (solute carrier family 5 member 2) This gene encodes a member of the sodium glucose cotransporter family which are sodium-dependent glucose transport proteins. The encoded protein is the major cotransporter involved in glucose reabsorption in the kidney. Mutations in this gene are associated with renal glucosuria. Two transcript variants, one protein-coding and one not, have been found for this gene. [provided by RefSeq, Feb 2015]

SLC5A2 links:

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ACMG classification

Classification made for transcript

Verdict is Pathogenic. Variant got 10 ACMG points.

PVS1

Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.

PP5

Variant 16-31489216-T-TCGGCGTGCCCAGCTTTCCTCTG is Pathogenic according to our data. Variant chr16-31489216-T-TCGGCGTGCCCAGCTTTCCTCTG is described in ClinVar as [Likely_pathogenic]. Clinvar id is 591299.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC5A2	NM_003041.4 link	c.1552_1573dupCCAGCTTTCCTCTGCGGCGTGC	p.His525ProfsTer49	frameshift_variant	Exon 12 of 14	ENST00000330498.4	NP_003032.1	P31639-1
SLC5A2	XM_006721072.5 link	c.1552_1573dupCCAGCTTTCCTCTGCGGCGTGC	p.His525ProfsTer49	frameshift_variant	Exon 12 of 13		XP_006721135.3	Q8WY15
SLC5A2	XM_024450402.2 link	c.1232_1253dupCCAGCTTTCCTCTGCGGCGTGC	p.Leu419GlnfsTer79	frameshift_variant	Exon 10 of 11		XP_024306170.2
SLC5A2	NR_130783.2 link	n.1246_1267dupCCAGCTTTCCTCTGCGGCGTGC		non_coding_transcript_exon_variant	Exon 10 of 12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
SLC5A2	ENST00000330498.4 link	c.1552_1573dupCCAGCTTTCCTCTGCGGCGTGC	p.His525ProfsTer49	frameshift_variant	Exon 12 of 14	1	NM_003041.4	ENSP00000327943.3	P31639-1
SLC5A2	ENST00000419665.6 link	n.1232_1253dupCCAGCTTTCCTCTGCGGCGTGC		non_coding_transcript_exon_variant	Exon 10 of 12	1		ENSP00000410601.2	P31639-2
SLC5A2	ENST00000568188.1 link	n.923_944dupCCAGCTTTCCTCTGCGGCGTGC		non_coding_transcript_exon_variant	Exon 3 of 3	2
SLC5A2	ENST00000568891.1 link	n.384_405dupCCAGCTTTCCTCTGCGGCGTGC		non_coding_transcript_exon_variant	Exon 2 of 4	5

Frequencies

GnomAD3 genomes

AF:

0.0000263

AC:

AN:

152208

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000965

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1457990

Hom.:

Cov.:

AF XY:

0.00000276

AC XY:

AN XY:

725530

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000224

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

AF:

0.0000263

AC:

AN:

152208

Hom.:

Cov.:

AF XY:

0.0000403

AC XY:

AN XY:

74362

show subpopulations

Gnomad4 AFR

AF:

0.0000965

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

ClinVar

Significance: Likely pathogenic

Submissions summary: Pathogenic:1Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Familial renal glucosuria

Pathogenic:1

Apr 13, 2024

Fulgent Genetics, Fulgent Genetics

Significance: Likely pathogenic

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided

Uncertain:1

Sep 16, 2018

Gharavi Laboratory, Columbia University

Significance: Uncertain significance

Review Status: no assertion criteria provided

Collection Method: research

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over