chr12-39604342-T-C

Position:

• chr12-39604342-T-C

Variant summary

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

The ENST00000308666.4(ABCD2):​c.1406-336A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.123 in 151,642 control chromosomes in the GnomAD database, including 1,179 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 0.12 (1179 hom., cov: 32)
• Consequence: ABCD2 ENST00000308666.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.322

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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.148 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ABCD2	NM_005164.4	c.1406-336A>G		intron_variant		ENST00000308666.4	NP_005155.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ABCD2	ENST00000308666.4	c.1406-336A>G		intron_variant		1	NM_005164.4	ENSP00000310688	P1

Frequencies

GnomAD3 genomes AF: 0.123 AC: 18625 AN: 151526 Hom.: 1174 Cov.: 32

Gnomad AFR AF: 0.133

Gnomad AMI AF: 0.0648

Gnomad AMR AF: 0.105

Gnomad ASJ AF: 0.152

Gnomad EAS AF: 0.157

Gnomad SAS AF: 0.0923

Gnomad FIN AF: 0.103

Gnomad MID AF: 0.158

Gnomad NFE AF: 0.122

Gnomad OTH AF: 0.135

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

GnomAD4 genome AF: 0.123 AC: 18647 AN: 151642 Hom.: 1179 Cov.: 32 AF XY: 0.122 AC XY: 9040 AN XY: 74102

Gnomad4 AFR AF: 0.133

Gnomad4 AMR AF: 0.105

Gnomad4 ASJ AF: 0.152

Gnomad4 EAS AF: 0.157

Gnomad4 SAS AF: 0.0918

Gnomad4 FIN AF: 0.103

Gnomad4 NFE AF: 0.122

Gnomad4 OTH AF: 0.138

Alfa AF: 0.120 Hom.: 528

Bravo AF: 0.124

Asia WGS AF: 0.137 AC: 473 AN: 3458

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	2.0
DANN	Benign	0.72

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: rs12227668; hg19: chr12-39998144;