2-43774077-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
• Publications: 5 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]

DYNC2LI1 Gene-Disease associations (from GenCC):

• short-rib thoracic dysplasia 15 with polydactyly

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P
• Ellis-van Creveld syndrome

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• Jeune syndrome

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016008.4. 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_016008.4	MANE Select	c.-62C>T		5_prime_UTR	Exon 1 of 13	NP_057092.2
	DYNC2LI1	NM_001348913.2		c.-62C>T		5_prime_UTR	Exon 1 of 14	NP_001335842.1
	DYNC2LI1	NM_001348912.2		c.-62C>T		5_prime_UTR	Exon 1 of 14	NP_001335841.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DYNC2LI1	ENST00000260605.12	TSL:1 MANE Select	c.-62C>T		5_prime_UTR	Exon 1 of 13	ENSP00000260605.8	Q8TCX1-1
	DYNC2LI1	ENST00000406852.7	TSL:1	c.-62C>T		5_prime_UTR	Exon 1 of 6	ENSP00000385738.3	Q8TCX1-4
	DYNC2LI1	ENST00000398823.6	TSL:1	c.-62C>T		5_prime_UTR	Exon 1 of 6	ENSP00000381804.2	Q8TCX1-5

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

African (AFR) AF: 0.119 AC: 3962 AN: 33278

American (AMR) AF: 0.0211 AC: 936 AN: 44334

Ashkenazi Jewish (ASJ) AF: 0.0264 AC: 686 AN: 26014

East Asian (EAS) AF: 0.0000254 AC: 1 AN: 39396

South Asian (SAS) AF: 0.0185 AC: 1581 AN: 85230

European-Finnish (FIN) AF: 0.0179 AC: 939 AN: 52504

Middle Eastern (MID) AF: 0.0256 AC: 147 AN: 5748

European-Non Finnish (NFE) AF: 0.0191 AC: 21183 AN: 1108714

Other (OTH) 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

African (AFR) AF: 0.111 AC: 4603 AN: 41568

American (AMR) AF: 0.0231 AC: 354 AN: 15310

Ashkenazi Jewish (ASJ) AF: 0.0277 AC: 96 AN: 3470

East Asian (EAS) AF: 0.000386 AC: 2 AN: 5176

South Asian (SAS) AF: 0.0203 AC: 98 AN: 4828

European-Finnish (FIN) AF: 0.0194 AC: 206 AN: 10622

Middle Eastern (MID) AF: 0.0306 AC: 9 AN: 294

European-Non Finnish (NFE) AF: 0.0208 AC: 1412 AN: 68028

Other (OTH) AF: 0.0402 AC: 85 AN: 2112

Alfa AF: 0.0393 Hom.: 166

Bravo AF: 0.0480

Asia WGS AF: 0.0170 AC: 59 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	6.4
DANN	Benign	0.82
PhyloP100		-0.81
PromoterAI		-0.14	Neutral
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

Other links and lift over

dbSNP: rs114189357; hg19: chr2-44001216;