rs386833505

chr5-149977699-C-Gchr5-149977699-C-T

Variant summary

Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1 PM2 PP5_Moderate

The NM_000112.4(SLC26A2):c.47C>G(p.Ser16Ter) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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)
• Consequence: SLC26A2 NM_000112.4 stop_gained
• Clinical Significance: Likely pathogenic criteria provided, single submitter P:2
• Conservation: PhyloP100: 2.08

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]

ACMG classification

Verdict is Pathogenic. Variant got 12 ACMG points.

• PVS1: Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant is located in the 3'-most 50 bp of the penultimate exon, not predicted to undergo nonsense mediated mRNA decay. There are 133 pathogenic variants in the truncated region.
• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 5-149977699-C-G is Pathogenic according to our data. Variant chr5-149977699-C-G is described in ClinVar as [Likely_pathogenic]. Clinvar id is 56024.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr5-149977699-C-G is described in Lovd as [Pathogenic].

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC26A2	NM_000112.4	c.47C>G	p.Ser16Ter	stop_gained	2/3	ENST00000286298.5
SLC26A2	XM_017009191.3	c.47C>G	p.Ser16Ter	stop_gained	2/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC26A2	ENST00000286298.5	c.47C>G	p.Ser16Ter	stop_gained	2/3	1	NM_000112.4	P1
SLC26A2	ENST00000433184.1	c.47C>G	p.Ser16Ter	stop_gained	3/3	4
SLC26A2	ENST00000690410.1	n.279C>G		non_coding_transcript_exon_variant	2/2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Significance: Likely pathogenic

Submissions summary: Pathogenic:2

Revision: criteria provided, single submitter

Submissions by phenotype

Achondrogenesis, type IB Pathogenic:1

Likely pathogenic, criteria provided, single submitter

clinical testing

Baylor Genetics

Jun 06, 2023

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Diastrophic dysplasia Pathogenic:1

Likely pathogenic, no assertion criteria provided

literature only

Juha Muilu Group; Institute for Molecular Medicine Finland (FIMM)

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.63	D
BayesDel_noAF	Uncertain	0.050
Cadd	Pathogenic	34
Dann	Uncertain	0.98
Eigen	Uncertain	0.34
Eigen_PC	Benign	0.033
FATHMM_MKL	Benign	0.19	N
MutationTaster	Benign	1.0	A
Vest4		0.67
GERP RS		3.4

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

Other links and lift over

dbSNP: rs386833505; hg19: chr5-149357262;