rs245051

Positions:

• chr5-149966412-A-G
• chr5-149966412-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000112.4(SLC26A2):​c.-26+5433A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.512 in 152,018 control chromosomes in the GnomAD database, including 21,348 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.51 (21348 hom., cov: 32)
• Consequence: SLC26A2 NM_000112.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.595

Genes affected

SLC26A2 (HGNC:10994): (solute carrier family 26 member 2) The diastrophic dysplasia sulfate transporter is a transmembrane glycoprotein implicated in the pathogenesis of several human chondrodysplasias. It apparently is critical in cartilage for sulfation of proteoglycans and matrix organization. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.7 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC26A2	NM_000112.4	c.-26+5433A>G		intron_variant		ENST00000286298.5	NP_000103.2
SLC26A2	XM_017009191.3	c.-26+5433A>G		intron_variant			XP_016864680.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC26A2	ENST00000286298.5	c.-26+5433A>G		intron_variant		1	NM_000112.4	ENSP00000286298	P1
SLC26A2	ENST00000433184.1	c.-26+4140A>G		intron_variant		4		ENSP00000405496
SLC26A2	ENST00000690410.1	n.207+5433A>G		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.512 AC: 77809 AN: 151902 Hom.: 21312 Cov.: 32

Gnomad AFR AF: 0.707

Gnomad AMI AF: 0.491

Gnomad AMR AF: 0.567

Gnomad ASJ AF: 0.413

Gnomad EAS AF: 0.481

Gnomad SAS AF: 0.501

Gnomad FIN AF: 0.385

Gnomad MID AF: 0.538

Gnomad NFE AF: 0.410

Gnomad OTH AF: 0.509

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.512 AC: 77901 AN: 152018 Hom.: 21348 Cov.: 32 AF XY: 0.513 AC XY: 38110 AN XY: 74272

Gnomad4 AFR AF: 0.707

Gnomad4 AMR AF: 0.567

Gnomad4 ASJ AF: 0.413

Gnomad4 EAS AF: 0.481

Gnomad4 SAS AF: 0.500

Gnomad4 FIN AF: 0.385

Gnomad4 NFE AF: 0.410

Gnomad4 OTH AF: 0.512

Alfa AF: 0.426 Hom.: 25934

Bravo AF: 0.535

Asia WGS AF: 0.523 AC: 1819 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	6.0
DANN	Benign	0.70

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: rs245051; hg19: chr5-149345975;