2-43783481-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_016008.4(DYNC2LI1):c.127-39G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.341 in 1,436,768 control chromosomes in the GnomAD database, including 90,204 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.42 (15598 hom., cov: 32)
  • Exomes 𝑓: 0.33 (74606 hom.)
• Consequence: DYNC2LI1 NM_016008.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0840

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 2-43783481-G-A is Benign according to our data. Variant chr2-43783481-G-A is described in ClinVar as [Benign]. Clinvar id is 1294721.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.656 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DYNC2LI1	NM_016008.4	c.127-39G>A		intron_variant		ENST00000260605.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DYNC2LI1	ENST00000260605.12	c.127-39G>A		intron_variant		1	NM_016008.4	P4

Frequencies

GnomAD3 genomes AF: 0.424 AC: 64409 AN: 151890 Hom.: 15549 Cov.: 32

Gnomad AFR AF: 0.662

Gnomad AMI AF: 0.215

Gnomad AMR AF: 0.453

Gnomad ASJ AF: 0.341

Gnomad EAS AF: 0.174

Gnomad SAS AF: 0.462

Gnomad FIN AF: 0.298

Gnomad MID AF: 0.433

Gnomad NFE AF: 0.316

Gnomad OTH AF: 0.410

GnomAD3 exomes AF: 0.358 AC: 66464 AN: 185582 Hom.: 13074 AF XY: 0.356 AC XY: 36366 AN XY: 102088

Gnomad AFR exome AF: 0.667

Gnomad AMR exome AF: 0.464

Gnomad ASJ exome AF: 0.331

Gnomad EAS exome AF: 0.164

Gnomad SAS exome AF: 0.463

Gnomad FIN exome AF: 0.295

Gnomad NFE exome AF: 0.320

Gnomad OTH exome AF: 0.348

GnomAD4 exome AF: 0.331 AC: 425833 AN: 1284760 Hom.: 74606 Cov.: 19 AF XY: 0.335 AC XY: 215576 AN XY: 643782

Gnomad4 AFR exome AF: 0.669

Gnomad4 AMR exome AF: 0.451

Gnomad4 ASJ exome AF: 0.338

Gnomad4 EAS exome AF: 0.162

Gnomad4 SAS exome AF: 0.466

Gnomad4 FIN exome AF: 0.305

Gnomad4 NFE exome AF: 0.316

Gnomad4 OTH exome AF: 0.344

GnomAD4 genome AF: 0.424 AC: 64509 AN: 152008 Hom.: 15598 Cov.: 32 AF XY: 0.422 AC XY: 31376 AN XY: 74300

Gnomad4 AFR AF: 0.663

Gnomad4 AMR AF: 0.453

Gnomad4 ASJ AF: 0.341

Gnomad4 EAS AF: 0.173

Gnomad4 SAS AF: 0.460

Gnomad4 FIN AF: 0.298

Gnomad4 NFE AF: 0.316

Gnomad4 OTH AF: 0.412

Alfa AF: 0.355 Hom.: 2764

Bravo AF: 0.443

Asia WGS AF: 0.355 AC: 1233 AN: 3470

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 11, 2021

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
Cadd	Benign	8.0
Dann	Benign	0.66

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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

Other links and lift over

dbSNP: rs3815995; hg19: chr2-44010620; COSMIC: COSV53184706;