rs8073

Variant names:

• chr5-149982837-T-G
• rs8073
• NM_000112.4:c.*1024T>G

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_000112.4(SLC26A2):​c.*1024T>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.224 in 152,064 control chromosomes in the GnomAD database, including 3,904 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.22 (3903 hom., cov: 32)
  • Exomes 𝑓: 1.0 (1 hom.)
• Consequence: SLC26A2 NM_000112.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:5
• Conservation: PhyloP100: -0.596
• Publications: 11 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: ClinGen, G2P, Ambry Genetics, Orphanet
• atelosteogenesis type II

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

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Ambry Genetics, ClinGen, Labcorp Genetics (formerly Invitae), 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
• SLC26A2-related skeletal dysplasia

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
• skeletal dysplasia

  Inheritance: AR Classification: STRONG Submitted by: PanelApp Australia

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 5-149982837-T-G is Benign according to our data. Variant chr5-149982837-T-G is described in ClinVar as Benign. ClinVar VariationId is 352046.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.317 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.*1024T>G		3_prime_UTR	Exon 3 of 3	NP_000103.2	P50443

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC26A2	ENST00000286298.5	TSL:1 MANE Select	c.*1024T>G		3_prime_UTR	Exon 3 of 3	ENSP00000286298.4	P50443
	SLC26A2	ENST00000862081.1		c.*1024T>G		3_prime_UTR	Exon 4 of 4	ENSP00000532140.1
	SLC26A2	ENST00000862082.1		c.*1024T>G		3_prime_UTR	Exon 3 of 3	ENSP00000532141.1

Frequencies

GnomAD3 genomes AF: 0.224 AC: 34041 AN: 151942 Hom.: 3898 Cov.: 32

Gnomad AFR AF: 0.242

Gnomad AMI AF: 0.228

Gnomad AMR AF: 0.231

Gnomad ASJ AF: 0.217

Gnomad EAS AF: 0.290

Gnomad SAS AF: 0.331

Gnomad FIN AF: 0.183

Gnomad MID AF: 0.329

Gnomad NFE AF: 0.204

Gnomad OTH AF: 0.242

GnomAD4 exome AF: 1.00 AC: 2 AN: 2 Hom.: 1 Cov.: 0 AF XY: 1.00 AC XY: 2 AN XY: 2

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 1.00 AC: 2 AN: 2

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.224 AC: 34068 AN: 152062 Hom.: 3903 Cov.: 32 AF XY: 0.226 AC XY: 16787 AN XY: 74354

African (AFR) AF: 0.242 AC: 10032 AN: 41446

American (AMR) AF: 0.231 AC: 3527 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.217 AC: 752 AN: 3470

East Asian (EAS) AF: 0.290 AC: 1499 AN: 5170

South Asian (SAS) AF: 0.330 AC: 1594 AN: 4826

European-Finnish (FIN) AF: 0.183 AC: 1940 AN: 10580

Middle Eastern (MID) AF: 0.337 AC: 99 AN: 294

European-Non Finnish (NFE) AF: 0.204 AC: 13898 AN: 67980

Other (OTH) AF: 0.246 AC: 519 AN: 2110

Alfa AF: 0.219 Hom.: 6252

Bravo AF: 0.228

Asia WGS AF: 0.293 AC: 1015 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	Achondrogenesis, type IB (1)
-	-	1	Atelosteogenesis type II (1)
-	-	1	Diastrophic dysplasia (1)
-	-	1	Multiple epiphyseal dysplasia type 4 (1)
-	-	1	Sulfate transporter-related osteochondrodysplasia (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	3.3
DANN	Benign	0.48
PhyloP100		-0.60
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: rs8073; hg19: chr5-149362400;