Genetic Variant NM_000112.4: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:

Genome browser will be placed here

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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