Genetic Variant NM_000112.4:c.-25-6543T>C (chr5-149971085-T-C) – 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.-25-6543T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.273 in 152,144 control chromosomes in the GnomAD database, including 5,713 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 0.27 ( 5713 hom., cov: 32)

Consequence

SLC26A2
NM_000112.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.591

Publications

12 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=-0.92).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.394 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC26A2	NM_000112.4 link	c.-25-6543T>C		intron_variant	Intron 1 of 2	ENST00000286298.5	NP_000103.2	P50443
SLC26A2	XM_017009191.3 link	c.-25-6543T>C		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.-25-6543T>C	intron_variant	Intron 1 of 2	1	NM_000112.4	ENSP00000286298.4	P50443
SLC26A2	ENST00000433184.1 link	c.-25-6543T>C	intron_variant	Intron 2 of 2	4		ENSP00000405496.1	C9JAN6
SLC26A2	ENST00000690410.1 link	n.208-6543T>C	intron_variant	Intron 1 of 1

Frequencies

GnomAD3 genomes

AF:

0.273

AC:

41441

AN:

152026

Hom.:

5696

Cov.:

show subpopulations

Gnomad AFR

AF:

0.268

Gnomad AMI

AF:

0.368

Gnomad AMR

AF:

0.256

Gnomad ASJ

AF:

0.232

Gnomad EAS

AF:

0.377

Gnomad SAS

AF:

0.410

Gnomad FIN

AF:

0.239

Gnomad MID

AF:

0.294

Gnomad NFE

AF:

0.267

Gnomad OTH

AF:

0.291

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

GnomAD4 genome

AF:

0.273

AC:

41509

AN:

152144

Hom.:

5713

Cov.:

AF XY:

0.274

AC XY:

20411

AN XY:

74394

show subpopulations

African (AFR)

AF:

0.269

AC:

11147

AN:

41500

American (AMR)

AF:

0.256

AC:

3913

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.232

AC:

805

AN:

3466

East Asian (EAS)

AF:

0.377

AC:

1952

AN:

5174

South Asian (SAS)

AF:

0.409

AC:

1970

AN:

4818

European-Finnish (FIN)

AF:

0.239

AC:

2534

AN:

10590

Middle Eastern (MID)

AF:

0.310

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.267

AC:

18136

AN:

67990

Other (OTH)

AF:

0.296

AC:

626

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1600

3200

4800

6400

8000

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

438

876

1314

1752

2190

<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:

0.273

Hom.:

24504

Bravo

AF:

0.274

Asia WGS

AF:

0.401

AC:

1391

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

6.9

(source)

DANN

Benign

0.65

PhyloP100

-0.59

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