chr2-43774077-C-T

Variant names:

• chr2-43774077-C-T
• rs114189357
• NM_016008.4:c.-62C>T

Variant summary

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

The NM_016008.4(DYNC2LI1):​c.-62C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0235 in 1,607,612 control chromosomes in the GnomAD database, including 823 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.045 (303 hom., cov: 32)
  • Exomes 𝑓: 0.021 (520 hom.)
• Consequence: DYNC2LI1 NM_016008.4 5_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.808

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]

LOC105374571 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 2-43774077-C-T is Benign according to our data. Variant chr2-43774077-C-T is described in ClinVar as [Benign]. Clinvar id is 1246768.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.108 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DYNC2LI1	NM_016008.4	c.-62C>T		5_prime_UTR_variant	Exon 1 of 13	ENST00000260605.12	NP_057092.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DYNC2LI1	ENST00000260605	c.-62C>T		5_prime_UTR_variant	Exon 1 of 13	1	NM_016008.4	ENSP00000260605.8

Frequencies

GnomAD3 genomes AF: 0.0451 AC: 6859 AN: 152202 Hom.: 301 Cov.: 32

Gnomad AFR AF: 0.111

Gnomad AMI AF: 0.00219

Gnomad AMR AF: 0.0232

Gnomad ASJ AF: 0.0277

Gnomad EAS AF: 0.000386

Gnomad SAS AF: 0.0203

Gnomad FIN AF: 0.0194

Gnomad MID AF: 0.0348

Gnomad NFE AF: 0.0208

Gnomad OTH AF: 0.0407

GnomAD4 exome AF: 0.0212 AC: 30856 AN: 1455292 Hom.: 520 Cov.: 30 AF XY: 0.0213 AC XY: 15385 AN XY: 723608

Gnomad4 AFR exome AF: 0.119 AC: 3962 AN: 33278

Gnomad4 AMR exome AF: 0.0211 AC: 936 AN: 44334

Gnomad4 ASJ exome AF: 0.0264 AC: 686 AN: 26014

Gnomad4 EAS exome AF: 0.0000254 AC: 1 AN: 39396

Gnomad4 SAS exome AF: 0.0185 AC: 1581 AN: 85230

Gnomad4 FIN exome AF: 0.0179 AC: 939 AN: 52504

Gnomad4 NFE exome AF: 0.0191 AC: 21183 AN: 1108714

Gnomad4 Remaining exome AF: 0.0237 AC: 1421 AN: 60074

GnomAD4 genome AF: 0.0451 AC: 6867 AN: 152320 Hom.: 303 Cov.: 32 AF XY: 0.0444 AC XY: 3303 AN XY: 74474

Gnomad4 AFR AF: 0.111 AC: 0.110734 AN: 0.110734

Gnomad4 AMR AF: 0.0231 AC: 0.0231221 AN: 0.0231221

Gnomad4 ASJ AF: 0.0277 AC: 0.0276657 AN: 0.0276657

Gnomad4 EAS AF: 0.000386 AC: 0.000386399 AN: 0.000386399

Gnomad4 SAS AF: 0.0203 AC: 0.0202983 AN: 0.0202983

Gnomad4 FIN AF: 0.0194 AC: 0.0193937 AN: 0.0193937

Gnomad4 NFE AF: 0.0208 AC: 0.0207562 AN: 0.0207562

Gnomad4 OTH AF: 0.0402 AC: 0.0402462 AN: 0.0402462

Alfa AF: 0.0393 Hom.: 166

Bravo AF: 0.0480

Asia WGS AF: 0.0170 AC: 59 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

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Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

May 12, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	6.4
DANN	Benign	0.82
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.0
Mutation Taster		=299/1	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

Publications

LitVar

Other links and lift over

dbSNP: rs114189357; hg19: chr2-44001216;