rs1835815

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr2-43803510-C-G
• chr2-43803510-C-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_016008.4(DYNC2LI1):​c.803-1132C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DYNC2LI1	NM_016008.4	c.803-1132C>G		intron_variant	Intron 10 of 12	ENST00000260605.12	NP_057092.2
DYNC2LI1	NM_001348913.2	c.806-1132C>G		intron_variant	Intron 10 of 13		NP_001335842.1
DYNC2LI1	NM_001348912.2	c.803-1132C>G		intron_variant	Intron 10 of 13		NP_001335841.1
DYNC2LI1	NM_001193464.2	c.806-1132C>G		intron_variant	Intron 10 of 12		NP_001180393.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DYNC2LI1	ENST00000260605.12	c.803-1132C>G		intron_variant	Intron 10 of 12	1	NM_016008.4	ENSP00000260605.8
DYNC2LI1	ENST00000605786.5	c.806-1132C>G		intron_variant	Intron 10 of 12	1		ENSP00000474032.1
DYNC2LI1	ENST00000378587.3	c.752-1132C>G		intron_variant	Intron 9 of 10	1		ENSP00000367850.3
DYNC2LI1	ENST00000482738.1	n.440-1132C>G		intron_variant	Intron 1 of 2	3

Frequencies

GnomAD3 genomes Cov.: 31

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

GnomAD4 genome Cov.: 31

Alfa AF: 0.00 Hom.: 24573

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	4.4
DANN	Benign	0.59
PhyloP100		0.021

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;