rs245056

Variant names:

• chr5-149961475-T-A
• rs245056
• NM_000112.4:c.-26+496T>A

Your query was ambiguous. Multiple possible variants found:

• chr5-149961475-T-A
• chr5-149961475-T-G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000112.4(SLC26A2):​c.-26+496T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.431 in 151,918 control chromosomes in the GnomAD database, including 14,353 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 0.43 (14353 hom., cov: 32)
• Consequence: SLC26A2 NM_000112.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.123
• Publications: 5 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: Orphanet, Ambry Genetics, G2P, 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: Labcorp Genetics (formerly Invitae), ClinGen, Ambry Genetics, Orphanet
• 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

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.523 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC26A2	NM_000112.4	MANE Select	c.-26+496T>A		intron	N/A	NP_000103.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC26A2	ENST00000286298.5	TSL:1 MANE Select	c.-26+496T>A		intron	N/A	ENSP00000286298.4
	SLC26A2	ENST00000433184.1	TSL:4	c.-306+496T>A		intron	N/A	ENSP00000405496.1
	SLC26A2	ENST00000690410.1		n.207+496T>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.431 AC: 65393 AN: 151800 Hom.: 14329 Cov.: 32

Gnomad AFR AF: 0.437

Gnomad AMI AF: 0.484

Gnomad AMR AF: 0.533

Gnomad ASJ AF: 0.409

Gnomad EAS AF: 0.481

Gnomad SAS AF: 0.498

Gnomad FIN AF: 0.374

Gnomad MID AF: 0.503

Gnomad NFE AF: 0.404

Gnomad OTH AF: 0.457

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

GnomAD4 genome AF: 0.431 AC: 65474 AN: 151918 Hom.: 14353 Cov.: 32 AF XY: 0.434 AC XY: 32225 AN XY: 74230

African (AFR) AF: 0.438 AC: 18118 AN: 41400

American (AMR) AF: 0.533 AC: 8145 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.409 AC: 1418 AN: 3466

East Asian (EAS) AF: 0.481 AC: 2474 AN: 5148

South Asian (SAS) AF: 0.496 AC: 2393 AN: 4822

European-Finnish (FIN) AF: 0.374 AC: 3945 AN: 10558

Middle Eastern (MID) AF: 0.520 AC: 153 AN: 294

European-Non Finnish (NFE) AF: 0.404 AC: 27412 AN: 67926

Other (OTH) AF: 0.461 AC: 975 AN: 2114

Alfa AF: 0.408 Hom.: 1599

Bravo AF: 0.445

Asia WGS AF: 0.500 AC: 1740 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	5.2
DANN	Benign	0.64
PhyloP100		0.12
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: rs245056; hg19: chr5-149341038;