NM_000112.4:c.-26+737A>G

Variant names:

• chr5-149961716-A-G
• rs245055
• NM_000112.4:c.-26+737A>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+737A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.212 in 151,944 control chromosomes in the GnomAD database, including 4,158 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 0.21 (4158 hom., cov: 32)
• Consequence: SLC26A2 NM_000112.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.97
• Publications: 6 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.379 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.-26+737A>G		intron	N/A	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.-26+737A>G		intron	N/A	ENSP00000286298.4	P50443
	SLC26A2	ENST00000862081.1		c.-196+737A>G		intron	N/A	ENSP00000532140.1
	SLC26A2	ENST00000862082.1		c.-26+78A>G		intron	N/A	ENSP00000532141.1

Frequencies

GnomAD3 genomes AF: 0.213 AC: 32276 AN: 151826 Hom.: 4156 Cov.: 32

Gnomad AFR AF: 0.0636

Gnomad AMI AF: 0.366

Gnomad AMR AF: 0.235

Gnomad ASJ AF: 0.236

Gnomad EAS AF: 0.374

Gnomad SAS AF: 0.394

Gnomad FIN AF: 0.238

Gnomad MID AF: 0.288

Gnomad NFE AF: 0.265

Gnomad OTH AF: 0.246

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

GnomAD4 genome AF: 0.212 AC: 32286 AN: 151944 Hom.: 4158 Cov.: 32 AF XY: 0.215 AC XY: 15981 AN XY: 74222

African (AFR) AF: 0.0634 AC: 2631 AN: 41480

American (AMR) AF: 0.235 AC: 3579 AN: 15240

Ashkenazi Jewish (ASJ) AF: 0.236 AC: 819 AN: 3468

East Asian (EAS) AF: 0.373 AC: 1928 AN: 5162

South Asian (SAS) AF: 0.394 AC: 1892 AN: 4808

European-Finnish (FIN) AF: 0.238 AC: 2505 AN: 10526

Middle Eastern (MID) AF: 0.303 AC: 89 AN: 294

European-Non Finnish (NFE) AF: 0.265 AC: 17982 AN: 67948

Other (OTH) AF: 0.250 AC: 529 AN: 2112

Alfa AF: 0.258 Hom.: 8472

Bravo AF: 0.205

Asia WGS AF: 0.353 AC: 1224 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.084
DANN	Benign	0.30
PhyloP100		-2.0
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: rs245055; hg19: chr5-149341279;