chr2-43774161-C-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_016008.4(DYNC2LI1):​c.8+15C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00169 in 1,613,840 control chromosomes in the GnomAD database, including 44 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0043 ( 8 hom., cov: 32)
Exomes 𝑓: 0.0014 ( 36 hom. )

Consequence

DYNC2LI1
NM_016008.4 intron

Scores

2

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.436
Variant links:
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.91).
BP6
Variant 2-43774161-C-G is Benign according to our data. Variant chr2-43774161-C-G is described in ClinVar as [Benign]. Clinvar id is 1642468.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BS1
Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.00433 (659/152318) while in subpopulation SAS AF= 0.0189 (91/4824). AF 95% confidence interval is 0.0157. There are 8 homozygotes in gnomad4. There are 329 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
High Homozygotes in GnomAd4 at 8 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
DYNC2LI1NM_016008.4 linkuse as main transcriptc.8+15C>G intron_variant ENST00000260605.12 NP_057092.2
LOC105374571XR_940033.2 linkuse as main transcriptn.9C>G non_coding_transcript_exon_variant 1/2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
DYNC2LI1ENST00000260605.12 linkuse as main transcriptc.8+15C>G intron_variant 1 NM_016008.4 ENSP00000260605 P4Q8TCX1-1

Frequencies

GnomAD3 genomes
AF:
0.00426
AC:
649
AN:
152200
Hom.:
6
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0129
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00105
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.0188
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000588
Gnomad OTH
AF:
0.00191
GnomAD3 exomes
AF:
0.00303
AC:
757
AN:
249918
Hom.:
10
AF XY:
0.00339
AC XY:
459
AN XY:
135294
show subpopulations
Gnomad AFR exome
AF:
0.0127
Gnomad AMR exome
AF:
0.000754
Gnomad ASJ exome
AF:
0.0000997
Gnomad EAS exome
AF:
0.0000546
Gnomad SAS exome
AF:
0.0168
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000620
Gnomad OTH exome
AF:
0.00131
GnomAD4 exome
AF:
0.00141
AC:
2067
AN:
1461522
Hom.:
36
Cov.:
30
AF XY:
0.00181
AC XY:
1316
AN XY:
727028
show subpopulations
Gnomad4 AFR exome
AF:
0.0125
Gnomad4 AMR exome
AF:
0.000805
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.000101
Gnomad4 SAS exome
AF:
0.0165
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000899
Gnomad4 OTH exome
AF:
0.00275
GnomAD4 genome
AF:
0.00433
AC:
659
AN:
152318
Hom.:
8
Cov.:
32
AF XY:
0.00442
AC XY:
329
AN XY:
74472
show subpopulations
Gnomad4 AFR
AF:
0.0131
Gnomad4 AMR
AF:
0.00105
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.0189
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000588
Gnomad4 OTH
AF:
0.00189
Alfa
AF:
0.00256
Hom.:
1
Bravo
AF:
0.00444
Asia WGS
AF:
0.0110
AC:
37
AN:
3478

ClinVar

Significance: Benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not provided Benign:2
Benign, criteria provided, single submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpJan 15, 2024- -
Benign, criteria provided, single submitternot providedBreakthrough Genomics, Breakthrough Genomics-- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.91
CADD
Benign
3.4
DANN
Benign
0.46

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs113218674; hg19: chr2-44001300; API