Variant 5-149977655-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PVS1_ModeratePM2PP5_Moderate

The NM_000112.4(SLC26A2):c.3G>T(p.Met1?) variant causes a start lost change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000686 in 1,457,848 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Likely pathogenic (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

SLC26A2
NM_000112.4 start_lost

Scores

Clinical Significance

Likely pathogenic criteria provided, single submitter P:1

Conservation

PhyloP100: 2.33

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 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_pathogenic. Variant got 6 ACMG points.

PVS1

Start lost variant, next in-frame start position is after 3 pathogenic variants. Next in-frame start position is after 261 CDS bases. Genomic position: 149977913. Lost 0.118 part of the original CDS.

PM2

Very rare variant in population databases, with high coverage;

PP5

Variant 5-149977655-G-T is Pathogenic according to our data. Variant chr5-149977655-G-T is described in ClinVar as [Likely_pathogenic]. Clinvar id is 550984.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC26A2	NM_000112.4 link	c.3G>T	p.Met1?	start_lost	Exon 2 of 3	ENST00000286298.5	NP_000103.2	P50443
SLC26A2	XM_017009191.3 link	c.3G>T	p.Met1?	start_lost	Exon 2 of 4		XP_016864680.1	P50443

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
SLC26A2	ENST00000286298.5 link	c.3G>T	p.Met1?	start_lost	Exon 2 of 3	1	NM_000112.4	ENSP00000286298.4	P50443
SLC26A2	ENST00000433184.1 link	c.3G>T	p.Met1?	start_lost	Exon 3 of 3	4		ENSP00000405496.1	C9JAN6
SLC26A2	ENST00000690410.1 link	n.235G>T		non_coding_transcript_exon_variant	Exon 2 of 2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.86e-7

AC:

AN:

1457848

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

725552

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.02e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Likely pathogenic

Submissions summary: Pathogenic:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Multiple epiphyseal dysplasia type 4

Pathogenic:1

Mar 22, 2017

Counsyl

Significance: Likely pathogenic

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Pathogenic

0.63

BayesDel_noAF

Pathogenic

0.43

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.11

T;.

Eigen

Uncertain

0.47

Eigen_PC

Uncertain

0.46

FATHMM_MKL

Uncertain

0.79

LIST_S2

Uncertain

0.90

D;.

M_CAP

Pathogenic

0.90

MetaRNN

Pathogenic

0.99

D;D

MetaSVM

Pathogenic

0.88

PROVEAN

Benign

-0.44

N;D

REVEL

Pathogenic

0.83

Sift

Pathogenic

0.0

D;.

Sift4G

Pathogenic

0.0

D;.

Polyphen

0.85

P;.

Vest4

0.95

MutPred

1.0

Gain of catalytic residue at M1 (P = 0.0634);Gain of catalytic residue at M1 (P = 0.0634);

MVP

0.97

ClinPred

0.83

GERP RS

4.8

Varity_R

0.77

gMVP

0.52

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over