5-149976512-T-G

Position:

• chr5-149976512-T-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000112.4(SLC26A2):​c.-25-1116T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.219 in 152,224 control chromosomes in the GnomAD database, including 4,411 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 0.22 (4411 hom., cov: 32)
• Consequence: SLC26A2 NM_000112.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0640

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.379 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC26A2	NM_000112.4	c.-25-1116T>G		intron_variant		ENST00000286298.5
SLC26A2	XM_017009191.3	c.-25-1116T>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC26A2	ENST00000286298.5	c.-25-1116T>G		intron_variant		1	NM_000112.4	P1
SLC26A2	ENST00000433184.1	c.-25-1116T>G		intron_variant		4
SLC26A2	ENST00000690410.1	n.208-1116T>G		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.219 AC: 33300 AN: 152104 Hom.: 4405 Cov.: 32

Gnomad AFR AF: 0.0655

Gnomad AMI AF: 0.377

Gnomad AMR AF: 0.242

Gnomad ASJ AF: 0.243

Gnomad EAS AF: 0.363

Gnomad SAS AF: 0.394

Gnomad FIN AF: 0.251

Gnomad MID AF: 0.328

Gnomad NFE AF: 0.274

Gnomad OTH AF: 0.252

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

GnomAD4 genome AF: 0.219 AC: 33316 AN: 152224 Hom.: 4411 Cov.: 32 AF XY: 0.222 AC XY: 16508 AN XY: 74428

Gnomad4 AFR AF: 0.0654

Gnomad4 AMR AF: 0.242

Gnomad4 ASJ AF: 0.243

Gnomad4 EAS AF: 0.363

Gnomad4 SAS AF: 0.394

Gnomad4 FIN AF: 0.251

Gnomad4 NFE AF: 0.274

Gnomad4 OTH AF: 0.258

Alfa AF: 0.125 Hom.: 263

Bravo AF: 0.210

Asia WGS AF: 0.363 AC: 1258 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	4.4
DANN	Benign	0.84

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: rs245081; hg19: chr5-149356075;