rs2278356

Variant names:

• chr2-43812736-A-C
• rs2278356
• ENST00000486512.5:n.2857T>G

Your query was ambiguous. Multiple possible variants found:

• chr2-43812736-A-C
• chr2-43812736-A-G
• chr2-43812736-A-T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The ENST00000486512.5(ABCG5):​n.2857T>G variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.415 in 197,730 control chromosomes in the GnomAD database, including 19,353 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.44 (16293 hom., cov: 32)
  • Exomes 𝑓: 0.34 (3060 hom.)
• Consequence: ABCG5 ENST00000486512.5 non_coding_transcript_exon
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -3.67
• Publications: 13 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BP6: Variant 2-43812736-A-C is Benign according to our data. Variant chr2-43812736-A-C is described in ClinVar as Benign. ClinVar VariationId is 336031.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.658 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ABCG5	NM_022436.3	c.*380T>G		3_prime_UTR_variant	Exon 13 of 13	ENST00000405322.8	NP_071881.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ABCG5	ENST00000486512.5	n.2857T>G		non_coding_transcript_exon_variant	Exon 9 of 9	1
ABCG5	ENST00000405322.8	c.*380T>G		3_prime_UTR_variant	Exon 13 of 13	1	NM_022436.3	ENSP00000384513.2
ABCG5	ENST00000644754.1	n.2720T>G		non_coding_transcript_exon_variant	Exon 10 of 10
ABCG5	ENST00000409962.1	n.*107T>G		downstream_gene_variant		2

Frequencies

GnomAD3 genomes AF: 0.436 AC: 66283 AN: 151930 Hom.: 16244 Cov.: 32

Gnomad AFR AF: 0.664

Gnomad AMI AF: 0.215

Gnomad AMR AF: 0.463

Gnomad ASJ AF: 0.382

Gnomad EAS AF: 0.181

Gnomad SAS AF: 0.496

Gnomad FIN AF: 0.304

Gnomad MID AF: 0.497

Gnomad NFE AF: 0.333

Gnomad OTH AF: 0.422

GnomAD4 exome AF: 0.344 AC: 15701 AN: 45682 Hom.: 3060 Cov.: 0 AF XY: 0.351 AC XY: 8254 AN XY: 23500

African (AFR) AF: 0.651 AC: 569 AN: 874

American (AMR) AF: 0.465 AC: 1591 AN: 3418

Ashkenazi Jewish (ASJ) AF: 0.345 AC: 359 AN: 1042

East Asian (EAS) AF: 0.168 AC: 452 AN: 2692

South Asian (SAS) AF: 0.459 AC: 2556 AN: 5568

European-Finnish (FIN) AF: 0.285 AC: 618 AN: 2166

Middle Eastern (MID) AF: 0.396 AC: 61 AN: 154

European-Non Finnish (NFE) AF: 0.318 AC: 8703 AN: 27388

Other (OTH) AF: 0.333 AC: 792 AN: 2380

GnomAD4 genome AF: 0.437 AC: 66382 AN: 152048 Hom.: 16293 Cov.: 32 AF XY: 0.435 AC XY: 32313 AN XY: 74308

African (AFR) AF: 0.664 AC: 27547 AN: 41478

American (AMR) AF: 0.464 AC: 7090 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.382 AC: 1326 AN: 3468

East Asian (EAS) AF: 0.180 AC: 930 AN: 5172

South Asian (SAS) AF: 0.494 AC: 2378 AN: 4818

European-Finnish (FIN) AF: 0.304 AC: 3208 AN: 10544

Middle Eastern (MID) AF: 0.503 AC: 148 AN: 294

European-Non Finnish (NFE) AF: 0.333 AC: 22664 AN: 67964

Other (OTH) AF: 0.423 AC: 895 AN: 2114

Alfa AF: 0.364 Hom.: 17747

Bravo AF: 0.455

Asia WGS AF: 0.372 AC: 1296 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Apr 19, 2019

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is associated with the following publications: (PMID: 29066094) -

Sitosterolemia 1 Benign:1

Jan 12, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.050
DANN	Benign	0.46
PhyloP100		-3.7
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: rs2278356; hg19: chr2-44039875;