5-149977400-G-A

Position:

• chr5-149977400-G-A

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.-25-228G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.182 in 152,062 control chromosomes in the GnomAD database, including 2,834 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.18 (2834 hom., cov: 32)
• Consequence: SLC26A2 NM_000112.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0240

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=-0.9).
• BP6: Variant 5-149977400-G-A is Benign according to our data. Variant chr5-149977400-G-A is described in ClinVar as [Benign]. Clinvar id is 671455.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	Protein	UniProt
SLC26A2	NM_000112.4	c.-25-228G>A		intron_variant		ENST00000286298.5	NP_000103.2
SLC26A2	XM_017009191.3	c.-25-228G>A		intron_variant			XP_016864680.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC26A2	ENST00000286298.5	c.-25-228G>A		intron_variant		1	NM_000112.4	ENSP00000286298	P1
SLC26A2	ENST00000433184.1	c.-25-228G>A		intron_variant		4		ENSP00000405496
SLC26A2	ENST00000690410.1	n.208-228G>A		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.182 AC: 27637 AN: 151944 Hom.: 2823 Cov.: 32

Gnomad AFR AF: 0.258

Gnomad AMI AF: 0.116

Gnomad AMR AF: 0.284

Gnomad ASJ AF: 0.152

Gnomad EAS AF: 0.102

Gnomad SAS AF: 0.0669

Gnomad FIN AF: 0.134

Gnomad MID AF: 0.184

Gnomad NFE AF: 0.137

Gnomad OTH AF: 0.181

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

GnomAD4 genome AF: 0.182 AC: 27679 AN: 152062 Hom.: 2834 Cov.: 32 AF XY: 0.183 AC XY: 13612 AN XY: 74340

Gnomad4 AFR AF: 0.258

Gnomad4 AMR AF: 0.283

Gnomad4 ASJ AF: 0.152

Gnomad4 EAS AF: 0.102

Gnomad4 SAS AF: 0.0665

Gnomad4 FIN AF: 0.134

Gnomad4 NFE AF: 0.137

Gnomad4 OTH AF: 0.180

Alfa AF: 0.159 Hom.: 294

Bravo AF: 0.198

Asia WGS AF: 0.112 AC: 391 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	-0.90
CADD	Benign	5.4
DANN	Benign	0.37

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: rs3812007; hg19: chr5-149356963;