rs245076

Variant names:

• chr5-149971085-T-C
• rs245076
• NM_000112.4:c.-25-6543T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 12 publications found

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]

SLC26A2 Gene-Disease associations (from GenCC):

• achondrogenesis type IB

  Inheritance: AR Classification: DEFINITIVE, MODERATE, SUPPORTIVE Submitted by: G2P, Orphanet, Ambry Genetics, ClinGen
• atelosteogenesis type II

  Inheritance: AR Classification: DEFINITIVE, MODERATE, SUPPORTIVE Submitted by: Orphanet, ClinGen, Ambry Genetics
• diastrophic dysplasia

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: ClinGen, Labcorp Genetics (formerly Invitae), Orphanet, Ambry Genetics
• multiple epiphyseal dysplasia

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
• multiple epiphyseal dysplasia type 4

  Inheritance: AR Classification: DEFINITIVE, MODERATE, SUPPORTIVE Submitted by: Ambry Genetics, Orphanet, G2P
• SLC26A2-related skeletal dysplasia

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000112.4. 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
	SLC26A2	NM_000112.4	MANE Select	c.-25-6543T>C		intron	N/A	NP_000103.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC26A2	ENST00000286298.5	TSL:1 MANE Select	c.-25-6543T>C		intron	N/A	ENSP00000286298.4
	SLC26A2	ENST00000862081.1		c.-195-4369T>C		intron	N/A	ENSP00000532140.1
	SLC26A2	ENST00000862082.1		c.-25-6543T>C		intron	N/A	ENSP00000532141.1

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

African (AFR) AF: 0.269 AC: 11147 AN: 41500

American (AMR) AF: 0.256 AC: 3913 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.232 AC: 805 AN: 3466

East Asian (EAS) AF: 0.377 AC: 1952 AN: 5174

South Asian (SAS) AF: 0.409 AC: 1970 AN: 4818

European-Finnish (FIN) AF: 0.239 AC: 2534 AN: 10590

Middle Eastern (MID) AF: 0.310 AC: 91 AN: 294

European-Non Finnish (NFE) AF: 0.267 AC: 18136 AN: 67990

Other (OTH) AF: 0.296 AC: 626 AN: 2116

Alfa AF: 0.273 Hom.: 24504

Bravo AF: 0.274

Asia WGS AF: 0.401 AC: 1391 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	6.9
DANN	Benign	0.65
PhyloP100		-0.59
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs245076; hg19: chr5-149350648;