rs3792009

Positions:

• chr2-43810194-G-A
• chr2-43810194-G-T

Variant summary

Our verdict is Benign. Variant got -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

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DYNC2LI1	NM_001348913.2	c.997-187G>A		intron_variant			NP_001335842.1
DYNC2LI1	NM_001348912.2	c.994-187G>A		intron_variant			NP_001335841.1
ABCG5	XM_006712073.4	c.1763-3783C>T		intron_variant			XP_006712136.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt

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

Gnomad4 AFR AF: 0.340

Gnomad4 AMR AF: 0.276

Gnomad4 ASJ AF: 0.184

Gnomad4 EAS AF: 0.115

Gnomad4 SAS AF: 0.262

Gnomad4 FIN AF: 0.124

Gnomad4 NFE AF: 0.158

Gnomad4 OTH AF: 0.204

Alfa AF: 0.168 Hom.: 4927

Bravo AF: 0.236

Asia WGS AF: 0.185 AC: 646 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs3792009; hg19: chr2-44037333;