rs11172502

Positions:

• chr12-39538649-A-T

Variant summary

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

The XM_017018992.3(ABCD2):​c.2004-6589T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.068 in 152,074 control chromosomes in the GnomAD database, including 538 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 0.068 (538 hom., cov: 32)
• Consequence: ABCD2 XM_017018992.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.526

Genes affected

ABCD2 (HGNC:66): (ATP binding cassette subfamily D member 2) The protein encoded by this gene is a member of the superfamily of ATP-binding cassette (ABC) transporters. ABC proteins transport various molecules across extra- and intra-cellular membranes. ABC genes are divided into seven distinct subfamilies (ABC1, MDR/TAP, MRP, ALD, OABP, GCN20, White). This protein is a member of the ALD subfamily, which is involved in peroxisomal import of fatty acids and/or fatty acyl-CoAs in the organelle. All known peroxisomal ABC transporters are half transporters which require a partner half transporter molecule to form a functional homodimeric or heterodimeric transporter. The function of this peroxisomal membrane protein is unknown; however this protein is speculated to function as a dimerization partner of ABCD1 and/or other peroxisomal ABC transporters. Mutations in this gene have been observed in patients with adrenoleukodystrophy, a severe demyelinating disease. This gene has been identified as a candidate for a modifier gene, accounting for the extreme variation among adrenoleukodystrophy phenotypes. This gene is also a candidate for a complement group of Zellweger syndrome, a genetically heterogeneous disorder of peroxisomal biogenesis. [provided by RefSeq, Jul 2008]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.269 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ABCD2	XM_017018992.3	c.2004-6589T>A		intron_variant			XP_016874481.1
		n.39538649A>T		intergenic_region

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt

Frequencies

GnomAD3 genomes AF: 0.0680 AC: 10332 AN: 151956 Hom.: 535 Cov.: 32

Gnomad AFR AF: 0.0145

Gnomad AMI AF: 0.129

Gnomad AMR AF: 0.0928

Gnomad ASJ AF: 0.0464

Gnomad EAS AF: 0.239

Gnomad SAS AF: 0.282

Gnomad FIN AF: 0.0556

Gnomad MID AF: 0.0759

Gnomad NFE AF: 0.0691

Gnomad OTH AF: 0.0666

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

GnomAD4 genome AF: 0.0680 AC: 10335 AN: 152074 Hom.: 538 Cov.: 32 AF XY: 0.0725 AC XY: 5391 AN XY: 74346

Gnomad4 AFR AF: 0.0144

Gnomad4 AMR AF: 0.0929

Gnomad4 ASJ AF: 0.0464

Gnomad4 EAS AF: 0.239

Gnomad4 SAS AF: 0.281

Gnomad4 FIN AF: 0.0556

Gnomad4 NFE AF: 0.0691

Gnomad4 OTH AF: 0.0687

Alfa AF: 0.0649 Hom.: 60

Bravo AF: 0.0663

Asia WGS AF: 0.220 AC: 764 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	5.8
DANN	Benign	0.74

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs11172502; hg19: chr12-39932451;