2-43821207-C-T

Variant names:

• chr2-43821207-C-T
• rs10439467
• NM_022436.3:c.1464-1107G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_022436.3(ABCG5):​c.1464-1107G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0745 in 152,196 control chromosomes in the GnomAD database, including 576 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 0.074 (576 hom., cov: 32)
• Consequence: ABCG5 NM_022436.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.501
• Publications: 4 publications found

Genes affected

ABCG5 (HGNC:13886): (ATP binding cassette subfamily G member 5) 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 White subfamily. The protein encoded by this gene functions as a half-transporter to limit intestinal absorption and promote biliary excretion of sterols. It is expressed in a tissue-specific manner in the liver, colon, and intestine. This gene is tandemly arrayed on chromosome 2, in a head-to-head orientation with family member ABCG8. Mutations in this gene may contribute to sterol accumulation and atheroschlerosis, and have been observed in patients with sitosterolemia. [provided by RefSeq, Jul 2008]

DYNC2LI1 (HGNC:24595): (dynein cytoplasmic 2 light intermediate chain 1) This gene encodes a protein that is a component of the dynein-2 microtubule motor protein complex that plays a role in the retrograde transport of cargo in primary cilia via the intraflagellar transport system. This gene is ubiquitously expressed and its protein, which localizes to the axoneme and Golgi apparatus, interacts directly with the cytoplasmic dynein 2 heavy chain 1 protein to form part of the multi-protein dynein-2 complex. Mutations in this gene produce defects in the dynein-2 complex which result in several types of ciliopathy including short-rib thoracic dysplasia 15 with polydactyly (SRTD15). Alternative splicing results in multiple transcript variants encoding distinct isoforms. [provided by RefSeq, Feb 2017]

DYNC2LI1 Gene-Disease associations (from GenCC):

• short-rib thoracic dysplasia 15 with polydactyly

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae)
• Ellis-van Creveld syndrome

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• Jeune syndrome

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.18 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_022436.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ABCG5	NM_022436.3	MANE Select	c.1464-1107G>A		intron	N/A	NP_071881.1
	DYNC2LI1	NM_001348913.2		c.*16-6179C>T		intron	N/A	NP_001335842.1
	DYNC2LI1	NM_001348912.2		c.*16-6179C>T		intron	N/A	NP_001335841.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ABCG5	ENST00000405322.8	TSL:1 MANE Select	c.1464-1107G>A		intron	N/A	ENSP00000384513.2
	ABCG5	ENST00000486512.5	TSL:1	n.1985-1107G>A		intron	N/A
	ABCG5	ENST00000882115.1		c.1329-1107G>A		intron	N/A	ENSP00000552174.1

Frequencies

GnomAD3 genomes AF: 0.0744 AC: 11319 AN: 152078 Hom.: 572 Cov.: 32

Gnomad AFR AF: 0.0639

Gnomad AMI AF: 0.0241

Gnomad AMR AF: 0.185

Gnomad ASJ AF: 0.0837

Gnomad EAS AF: 0.0447

Gnomad SAS AF: 0.0663

Gnomad FIN AF: 0.0629

Gnomad MID AF: 0.0316

Gnomad NFE AF: 0.0613

Gnomad OTH AF: 0.0705

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

GnomAD4 genome AF: 0.0745 AC: 11336 AN: 152196 Hom.: 576 Cov.: 32 AF XY: 0.0760 AC XY: 5658 AN XY: 74424

African (AFR) AF: 0.0637 AC: 2645 AN: 41514

American (AMR) AF: 0.185 AC: 2834 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.0837 AC: 290 AN: 3464

East Asian (EAS) AF: 0.0448 AC: 232 AN: 5182

South Asian (SAS) AF: 0.0661 AC: 319 AN: 4826

European-Finnish (FIN) AF: 0.0629 AC: 666 AN: 10590

Middle Eastern (MID) AF: 0.0340 AC: 10 AN: 294

European-Non Finnish (NFE) AF: 0.0613 AC: 4167 AN: 68028

Other (OTH) AF: 0.0717 AC: 151 AN: 2106

Alfa AF: 0.0714 Hom.: 793

Bravo AF: 0.0851

Asia WGS AF: 0.0700 AC: 242 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.6
DANN	Benign	0.43
PhyloP100		-0.50
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs10439467; hg19: chr2-44048346;