rs245051

Variant names:

• chr5-149966412-A-G
• rs245051
• NM_000112.4:c.-26+5433A>G

Your query was ambiguous. Multiple possible variants found:

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

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+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
• Publications: 16 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=-0.93).
• 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 rank	MANE	Protein	UniProt
SLC26A2	NM_000112.4	c.-26+5433A>G		intron_variant	Intron 1 of 2	ENST00000286298.5	NP_000103.2
SLC26A2	XM_017009191.3	c.-26+5433A>G		intron_variant	Intron 1 of 3		XP_016864680.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC26A2	ENST00000286298.5	c.-26+5433A>G		intron_variant	Intron 1 of 2	1	NM_000112.4	ENSP00000286298.4
SLC26A2	ENST00000433184.1	c.-26+4140A>G		intron_variant	Intron 2 of 2	4		ENSP00000405496.1
SLC26A2	ENST00000690410.1	n.207+5433A>G		intron_variant	Intron 1 of 1

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

African (AFR) AF: 0.707 AC: 29311 AN: 41476

American (AMR) AF: 0.567 AC: 8655 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.413 AC: 1433 AN: 3468

East Asian (EAS) AF: 0.481 AC: 2486 AN: 5170

South Asian (SAS) AF: 0.500 AC: 2404 AN: 4812

European-Finnish (FIN) AF: 0.385 AC: 4059 AN: 10536

Middle Eastern (MID) AF: 0.548 AC: 161 AN: 294

European-Non Finnish (NFE) AF: 0.410 AC: 27865 AN: 67968

Other (OTH) AF: 0.512 AC: 1081 AN: 2112

Alfa AF: 0.441 Hom.: 61350

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
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: rs245051; hg19: chr5-149345975;