12-39604065-G-T

Position:

• chr12-39604065-G-T

Variant summary

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

The ENST00000308666.4(ABCD2):​c.1406-59C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.18 in 1,201,426 control chromosomes in the GnomAD database, including 24,542 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 0.27 (7207 hom., cov: 32)
  • Exomes 𝑓: 0.17 (17335 hom.)
• Consequence: ABCD2 ENST00000308666.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.169

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.511 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ABCD2	NM_005164.4	c.1406-59C>A		intron_variant		ENST00000308666.4	NP_005155.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ABCD2	ENST00000308666.4	c.1406-59C>A		intron_variant		1	NM_005164.4	ENSP00000310688	P1

Frequencies

GnomAD3 genomes AF: 0.265 AC: 40248 AN: 151682 Hom.: 7177 Cov.: 32

Gnomad AFR AF: 0.516

Gnomad AMI AF: 0.168

Gnomad AMR AF: 0.180

Gnomad ASJ AF: 0.183

Gnomad EAS AF: 0.177

Gnomad SAS AF: 0.153

Gnomad FIN AF: 0.157

Gnomad MID AF: 0.209

Gnomad NFE AF: 0.170

Gnomad OTH AF: 0.245

GnomAD4 exome AF: 0.168 AC: 175813 AN: 1049626 Hom.: 17335 AF XY: 0.166 AC XY: 89538 AN XY: 540012

Gnomad4 AFR exome AF: 0.518

Gnomad4 AMR exome AF: 0.123

Gnomad4 ASJ exome AF: 0.172

Gnomad4 EAS exome AF: 0.174

Gnomad4 SAS exome AF: 0.150

Gnomad4 FIN exome AF: 0.158

Gnomad4 NFE exome AF: 0.160

Gnomad4 OTH exome AF: 0.184

GnomAD4 genome AF: 0.266 AC: 40326 AN: 151800 Hom.: 7207 Cov.: 32 AF XY: 0.262 AC XY: 19453 AN XY: 74164

Gnomad4 AFR AF: 0.516

Gnomad4 AMR AF: 0.180

Gnomad4 ASJ AF: 0.183

Gnomad4 EAS AF: 0.177

Gnomad4 SAS AF: 0.153

Gnomad4 FIN AF: 0.157

Gnomad4 NFE AF: 0.170

Gnomad4 OTH AF: 0.248

Alfa AF: 0.131 Hom.: 311

Bravo AF: 0.279

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.82
DANN	Benign	0.29

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: rs12228617; hg19: chr12-39997867; COSMIC: COSV58050384;