chr2-43810194-G-A

Variant names:

• chr2-43810194-G-A
• rs3792009
• NM_001348913.2:c.997-187G>A

Variant summary

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

The NM_001348913.2(DYNC2LI1):​c.997-187G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.22 in 152,140 control chromosomes in the GnomAD database, including 4,294 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 0.22 (4294 hom., cov: 32)
• Consequence: DYNC2LI1 NM_001348913.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.373
• Publications: 7 publications found

Genes affected

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]

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]

ABCG5 Gene-Disease associations (from GenCC):

• sitosterolemia

  Inheritance: AR Classification: DEFINITIVE, SUPPORTIVE Submitted by: Orphanet, ClinGen
• sitosterolemia 1

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), Laboratory for Molecular Medicine
• sitosterolemia 2

  Inheritance: AR Classification: DEFINITIVE Submitted by: G2P

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.335 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001348913.2. 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
	DYNC2LI1	NM_001348913.2		c.997-187G>A		intron	N/A	NP_001335842.1
	DYNC2LI1	NM_001348912.2		c.994-187G>A		intron	N/A	NP_001335841.1
	DYNC2LI1	NM_016008.4	MANE Select	c.*427G>A		downstream_gene	N/A	NP_057092.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DYNC2LI1	ENST00000260605.12	TSL:1 MANE Select	c.*427G>A		downstream_gene	N/A	ENSP00000260605.8	Q8TCX1-1
	DYNC2LI1	ENST00000605786.5	TSL:1	c.*427G>A		downstream_gene	N/A	ENSP00000474032.1	Q8TCX1-2
	DYNC2LI1	ENST00000965103.1		c.*427G>A		downstream_gene	N/A	ENSP00000635162.1

Frequencies

GnomAD3 genomes AF: 0.220 AC: 33404 AN: 152022 Hom.: 4281 Cov.: 32

Gnomad AFR AF: 0.340

Gnomad AMI AF: 0.124

Gnomad AMR AF: 0.276

Gnomad ASJ AF: 0.184

Gnomad EAS AF: 0.115

Gnomad SAS AF: 0.263

Gnomad FIN AF: 0.124

Gnomad MID AF: 0.187

Gnomad NFE AF: 0.158

Gnomad OTH AF: 0.203

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

GnomAD4 genome AF: 0.220 AC: 33450 AN: 152140 Hom.: 4294 Cov.: 32 AF XY: 0.220 AC XY: 16338 AN XY: 74386

African (AFR) AF: 0.340 AC: 14108 AN: 41472

American (AMR) AF: 0.276 AC: 4219 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.184 AC: 638 AN: 3470

East Asian (EAS) AF: 0.115 AC: 595 AN: 5178

South Asian (SAS) AF: 0.262 AC: 1266 AN: 4824

European-Finnish (FIN) AF: 0.124 AC: 1308 AN: 10580

Middle Eastern (MID) AF: 0.187 AC: 55 AN: 294

European-Non Finnish (NFE) AF: 0.158 AC: 10719 AN: 68010

Other (OTH) AF: 0.204 AC: 429 AN: 2108

Alfa AF: 0.182 Hom.: 9750

Bravo AF: 0.236

Asia WGS AF: 0.185 AC: 646 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	9.4
DANN	Benign	0.81
PhyloP100		-0.37

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs3792009; hg19: chr2-44037333;