Variant chr12-39573859-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_005164.4(ABCD2):c.1878-18G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00833 in 1,603,096 control chromosomes in the GnomAD database, including 118 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0068 ( 7 hom., cov: 32)

Exomes 𝑓: 0.0085 ( 111 hom. )

Consequence

ABCD2
NM_005164.4 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:2

Conservation

PhyloP100: -0.0390

Variant links:

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]

ABCD2 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BP6

Variant 12-39573859-C-G is Benign according to our data. Variant chr12-39573859-C-G is described in ClinVar as [Benign]. Clinvar id is 559119.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.00685 (1042/152162) while in subpopulation SAS AF= 0.0247 (119/4824). AF 95% confidence interval is 0.0211. There are 7 homozygotes in gnomad4. There are 544 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 7 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ABCD2	NM_005164.4 linkuse as main transcript	c.1878-18G>C		intron_variant		ENST00000308666.4	NP_005155.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ABCD2	ENST00000308666.4 linkuse as main transcript	c.1878-18G>C		intron_variant		1	NM_005164.4	ENSP00000310688	P1

Frequencies

GnomAD3 genomes

AF:

0.00685

AC:

1041

AN:

152044

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00186

Gnomad AMI

AF:

0.0493

Gnomad AMR

AF:

0.00805

Gnomad ASJ

AF:

0.00778

Gnomad EAS

AF:

0.000963

Gnomad SAS

AF:

0.0244

Gnomad FIN

AF:

0.00255

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.00879

Gnomad OTH

AF:

0.00909

GnomAD3 exomes

AF:

0.00851

AC:

2070

AN:

243240

Hom.:

AF XY:

0.00959

AC XY:

1261

AN XY:

131458

show subpopulations

Gnomad AFR exome

AF:

0.000870

Gnomad AMR exome

AF:

0.00265

Gnomad ASJ exome

AF:

0.0110

Gnomad EAS exome

AF:

0.000608

Gnomad SAS exome

AF:

0.0272

Gnomad FIN exome

AF:

0.00252

Gnomad NFE exome

AF:

0.00870

Gnomad OTH exome

AF:

0.00898

GnomAD4 exome

AF:

0.00848

AC:

12306

AN:

1450934

Hom.:

111

Cov.:

AF XY:

0.00906

AC XY:

6538

AN XY:

721418

show subpopulations

Gnomad4 AFR exome

AF:

0.00100

Gnomad4 AMR exome

AF:

0.00279

Gnomad4 ASJ exome

AF:

0.00993

Gnomad4 EAS exome

AF:

0.000203

Gnomad4 SAS exome

AF:

0.0264

Gnomad4 FIN exome

AF:

0.00265

Gnomad4 NFE exome

AF:

0.00809

Gnomad4 OTH exome

AF:

0.00837

GnomAD4 genome

AF:

0.00685

AC:

1042

AN:

152162

Hom.:

Cov.:

AF XY:

0.00731

AC XY:

544

AN XY:

74384

show subpopulations

Gnomad4 AFR

AF:

0.00185

Gnomad4 AMR

AF:

0.00804

Gnomad4 ASJ

AF:

0.00778

Gnomad4 EAS

AF:

0.000965

Gnomad4 SAS

AF:

0.0247

Gnomad4 FIN

AF:

0.00255

Gnomad4 NFE

AF:

0.00879

Gnomad4 OTH

AF:

0.00900

Alfa

AF:

0.00687

Hom.:

Bravo

AF:

0.00637

Asia WGS

AF:

0.0120

AC:

AN:

3476

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, no assertion criteria provided	clinical testing	Mayo Clinic Laboratories, Mayo Clinic	Feb 06, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

1.4

DANN

Benign

0.53

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over