16-66727724-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_006141.3(DYNC1LI2):​c.1225G>A​(p.Gly409Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,461,796 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

DYNC1LI2
NM_006141.3 missense

Scores

2
17

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.16
Variant links:
Genes affected
DYNC1LI2 (HGNC:2966): (dynein cytoplasmic 1 light intermediate chain 2) Cytoplasmic dynein is a microtubule-associated motor protein (Hughes et al., 1995 [PubMed 7738094]). See DYNC1H1 (MIM 600112) for general information about dyneins.[supplied by OMIM, Mar 2008]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.11623371).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
DYNC1LI2NM_006141.3 linkuse as main transcriptc.1225G>A p.Gly409Ser missense_variant 11/13 ENST00000258198.7 NP_006132.1 O43237-1A0A024R6Z0Q63HJ8

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
DYNC1LI2ENST00000258198.7 linkuse as main transcriptc.1225G>A p.Gly409Ser missense_variant 11/131 NM_006141.3 ENSP00000258198.2 O43237-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.00000398
AC:
1
AN:
251294
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
135808
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000290
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000137
AC:
2
AN:
1461796
Hom.:
0
Cov.:
31
AF XY:
0.00
AC XY:
0
AN XY:
727202
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000224
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
8.99e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsJan 12, 2024The c.1225G>A (p.G409S) alteration is located in exon 11 (coding exon 11) of the DYNC1LI2 gene. This alteration results from a G to A substitution at nucleotide position 1225, causing the glycine (G) at amino acid position 409 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.067
BayesDel_addAF
Benign
-0.25
T
BayesDel_noAF
Benign
-0.52
CADD
Benign
21
DANN
Benign
0.96
DEOGEN2
Benign
0.014
T;.;T
Eigen
Benign
-0.24
Eigen_PC
Benign
-0.053
FATHMM_MKL
Benign
0.71
D
LIST_S2
Uncertain
0.91
D;D;D
M_CAP
Benign
0.0085
T
MetaRNN
Benign
0.12
T;T;T
MetaSVM
Benign
-0.99
T
MutationAssessor
Benign
-0.075
N;.;.
PrimateAI
Uncertain
0.55
T
PROVEAN
Benign
-0.35
N;N;.
REVEL
Benign
0.075
Sift
Benign
0.84
T;T;.
Sift4G
Benign
0.79
T;T;T
Polyphen
0.019
B;.;.
Vest4
0.13
MutPred
0.39
Gain of phosphorylation at G409 (P = 0.006);.;.;
MVP
0.48
MPC
0.63
ClinPred
0.67
D
GERP RS
3.3
Varity_R
0.038
gMVP
0.27

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: rs1448769365; hg19: chr16-66761627; API