rs245076

Positions:

• chr5-149971085-T-C

Variant summary

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

The NM_000112.4(SLC26A2):​c.-25-6543T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.273 in 152,144 control chromosomes in the GnomAD database, including 5,713 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 0.27 (5713 hom., cov: 32)
• Consequence: SLC26A2 NM_000112.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.591

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=-0.92).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.394 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC26A2	NM_000112.4	c.-25-6543T>C		intron_variant		ENST00000286298.5	NP_000103.2
SLC26A2	XM_017009191.3	c.-25-6543T>C		intron_variant			XP_016864680.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC26A2	ENST00000286298.5	c.-25-6543T>C		intron_variant		1	NM_000112.4	ENSP00000286298	P1
SLC26A2	ENST00000433184.1	c.-25-6543T>C		intron_variant		4		ENSP00000405496
SLC26A2	ENST00000690410.1	n.208-6543T>C		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.273 AC: 41441 AN: 152026 Hom.: 5696 Cov.: 32

Gnomad AFR AF: 0.268

Gnomad AMI AF: 0.368

Gnomad AMR AF: 0.256

Gnomad ASJ AF: 0.232

Gnomad EAS AF: 0.377

Gnomad SAS AF: 0.410

Gnomad FIN AF: 0.239

Gnomad MID AF: 0.294

Gnomad NFE AF: 0.267

Gnomad OTH AF: 0.291

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

GnomAD4 genome AF: 0.273 AC: 41509 AN: 152144 Hom.: 5713 Cov.: 32 AF XY: 0.274 AC XY: 20411 AN XY: 74394

Gnomad4 AFR AF: 0.269

Gnomad4 AMR AF: 0.256

Gnomad4 ASJ AF: 0.232

Gnomad4 EAS AF: 0.377

Gnomad4 SAS AF: 0.409

Gnomad4 FIN AF: 0.239

Gnomad4 NFE AF: 0.267

Gnomad4 OTH AF: 0.296

Alfa AF: 0.275 Hom.: 12111

Bravo AF: 0.274

Asia WGS AF: 0.401 AC: 1391 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	6.9
DANN	Benign	0.65

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: rs245076; hg19: chr5-149350648;