Genetic Variant SLC26A2:c.-25-1116T>G (chr5-149976512-T-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_000112.4(SLC26A2):c.-25-1116T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.219 in 152,224 control chromosomes in the GnomAD database, including 4,411 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 0.22 ( 4411 hom., cov: 32)

Consequence

SLC26A2
NM_000112.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0640

Publications

4 publications found

Variant links:

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

SLC26A2 links:

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ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.81).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.379 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC26A2	NM_000112.4 link	c.-25-1116T>G		intron_variant	Intron 1 of 2	ENST00000286298.5	NP_000103.2	P50443
SLC26A2	XM_017009191.3 link	c.-25-1116T>G		intron_variant	Intron 1 of 3		XP_016864680.1	P50443

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
SLC26A2	ENST00000286298.5 link	c.-25-1116T>G	intron_variant	Intron 1 of 2	1	NM_000112.4	ENSP00000286298.4	P50443
SLC26A2	ENST00000433184.1 link	c.-25-1116T>G	intron_variant	Intron 2 of 2	4		ENSP00000405496.1	C9JAN6
SLC26A2	ENST00000690410.1 link	n.208-1116T>G	intron_variant	Intron 1 of 1

Frequencies

GnomAD3 genomes

AF:

0.219

AC:

33300

AN:

152104

Hom.:

4405

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0655

Gnomad AMI

AF:

0.377

Gnomad AMR

AF:

0.242

Gnomad ASJ

AF:

0.243

Gnomad EAS

AF:

0.363

Gnomad SAS

AF:

0.394

Gnomad FIN

AF:

0.251

Gnomad MID

AF:

0.328

Gnomad NFE

AF:

0.274

Gnomad OTH

AF:

0.252

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

GnomAD4 genome

AF:

0.219

AC:

33316

AN:

152224

Hom.:

4411

Cov.:

AF XY:

0.222

AC XY:

16508

AN XY:

74428

show subpopulations

African (AFR)

AF:

0.0654

AC:

2718

AN:

41566

American (AMR)

AF:

0.242

AC:

3701

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.243

AC:

844

AN:

3470

East Asian (EAS)

AF:

0.363

AC:

1877

AN:

5176

South Asian (SAS)

AF:

0.394

AC:

1897

AN:

4820

European-Finnish (FIN)

AF:

0.251

AC:

2659

AN:

10594

Middle Eastern (MID)

AF:

0.344

AC:

101

AN:

294

European-Non Finnish (NFE)

AF:

0.274

AC:

18630

AN:

67984

Other (OTH)

AF:

0.258

AC:

545

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1277

2555

3832

5110

6387

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

368

736

1104

1472

1840

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.125

Hom.:

263

Bravo

AF:

0.210

Asia WGS

AF:

0.363

AC:

1258

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

4.4

(source)

DANN

Benign

0.84

PhyloP100

-0.064

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over