5-149977497-A-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_000112.4(SLC26A2):c.-25-131A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.153 in 667,342 control chromosomes in the GnomAD database, including 9,183 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.18 (2870 hom., cov: 32)
  • Exomes 𝑓: 0.14 (6313 hom.)
• Consequence: SLC26A2 NM_000112.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.25

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 Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 5-149977497-A-G is Benign according to our data. Variant chr5-149977497-A-G is described in ClinVar as [Benign]. Clinvar id is 671224.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.276 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC26A2	NM_000112.4	c.-25-131A>G		intron_variant		ENST00000286298.5
SLC26A2	XM_017009191.3	c.-25-131A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC26A2	ENST00000286298.5	c.-25-131A>G		intron_variant		1	NM_000112.4	P1
SLC26A2	ENST00000433184.1	c.-25-131A>G		intron_variant		4
SLC26A2	ENST00000690410.1	n.208-131A>G		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.183 AC: 27754 AN: 152018 Hom.: 2859 Cov.: 32

Gnomad AFR AF: 0.260

Gnomad AMI AF: 0.116

Gnomad AMR AF: 0.284

Gnomad ASJ AF: 0.152

Gnomad EAS AF: 0.102

Gnomad SAS AF: 0.0671

Gnomad FIN AF: 0.134

Gnomad MID AF: 0.184

Gnomad NFE AF: 0.137

Gnomad OTH AF: 0.182

GnomAD4 exome AF: 0.144 AC: 74010 AN: 515206 Hom.: 6313 AF XY: 0.138 AC XY: 38188 AN XY: 276762

Gnomad4 AFR exome AF: 0.265

Gnomad4 AMR exome AF: 0.324

Gnomad4 ASJ exome AF: 0.157

Gnomad4 EAS exome AF: 0.0881

Gnomad4 SAS exome AF: 0.0744

Gnomad4 FIN exome AF: 0.144

Gnomad4 NFE exome AF: 0.136

Gnomad4 OTH exome AF: 0.158

GnomAD4 genome AF: 0.183 AC: 27798 AN: 152136 Hom.: 2870 Cov.: 32 AF XY: 0.184 AC XY: 13678 AN XY: 74394

Gnomad4 AFR AF: 0.261

Gnomad4 AMR AF: 0.283

Gnomad4 ASJ AF: 0.152

Gnomad4 EAS AF: 0.102

Gnomad4 SAS AF: 0.0668

Gnomad4 FIN AF: 0.134

Gnomad4 NFE AF: 0.137

Gnomad4 OTH AF: 0.180

Alfa AF: 0.151 Hom.: 3158

Bravo AF: 0.199

Asia WGS AF: 0.106 AC: 371 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 14, 2018

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
Cadd	Benign	14
Dann	Benign	0.75

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: rs17110742; hg19: chr5-149357060; COSMIC: COSV53824677; COSMIC: COSV53824677;