2-43803510-C-T

Variant names:

• chr2-43803510-C-T
• rs1835815
• NM_016008.4:c.803-1132C>T

Variant summary

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

The NM_016008.4(DYNC2LI1):​c.803-1132C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.423 in 151,854 control chromosomes in the GnomAD database, including 15,501 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 0.42 (15501 hom., cov: 31)
• Consequence: DYNC2LI1 NM_016008.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0210
• Publications: 2 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: G2P, Labcorp Genetics (formerly Invitae)
• Ellis-van Creveld syndrome

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

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.656 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DYNC2LI1	NM_016008.4	MANE Select	c.803-1132C>T		intron	N/A	NP_057092.2
	DYNC2LI1	NM_001348913.2		c.806-1132C>T		intron	N/A	NP_001335842.1
	DYNC2LI1	NM_001348912.2		c.803-1132C>T		intron	N/A	NP_001335841.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DYNC2LI1	ENST00000260605.12	TSL:1 MANE Select	c.803-1132C>T		intron	N/A	ENSP00000260605.8
	DYNC2LI1	ENST00000605786.5	TSL:1	c.806-1132C>T		intron	N/A	ENSP00000474032.1
	DYNC2LI1	ENST00000378587.3	TSL:1	c.752-1132C>T		intron	N/A	ENSP00000367850.3

Frequencies

GnomAD3 genomes AF: 0.423 AC: 64178 AN: 151736 Hom.: 15451 Cov.: 31

Gnomad AFR AF: 0.662

Gnomad AMI AF: 0.215

Gnomad AMR AF: 0.449

Gnomad ASJ AF: 0.339

Gnomad EAS AF: 0.182

Gnomad SAS AF: 0.461

Gnomad FIN AF: 0.297

Gnomad MID AF: 0.430

Gnomad NFE AF: 0.314

Gnomad OTH AF: 0.408

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

GnomAD4 genome AF: 0.423 AC: 64279 AN: 151854 Hom.: 15501 Cov.: 31 AF XY: 0.421 AC XY: 31268 AN XY: 74204

African (AFR) AF: 0.662 AC: 27455 AN: 41442

American (AMR) AF: 0.449 AC: 6853 AN: 15248

Ashkenazi Jewish (ASJ) AF: 0.339 AC: 1172 AN: 3462

East Asian (EAS) AF: 0.181 AC: 936 AN: 5170

South Asian (SAS) AF: 0.459 AC: 2198 AN: 4790

European-Finnish (FIN) AF: 0.297 AC: 3124 AN: 10508

Middle Eastern (MID) AF: 0.429 AC: 126 AN: 294

European-Non Finnish (NFE) AF: 0.314 AC: 21353 AN: 67916

Other (OTH) AF: 0.410 AC: 866 AN: 2112

Alfa AF: 0.347 Hom.: 24573

Bravo AF: 0.443

Asia WGS AF: 0.359 AC: 1250 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	5.0
DANN	Benign	0.70
PhyloP100		0.021
Mutation Taster		=100/0	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: rs1835815; hg19: chr2-44030649;