Genetic Variant DYNC1LI1:p.Asp203His (chr3-32541168-C-G) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_016141.4(DYNC1LI1):c.607G>C(p.Asp203His) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,162 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Consequence

DYNC1LI1
NM_016141.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.57

Variant links:

Genes affected

DYNC1LI1 (HGNC:18745): (dynein cytoplasmic 1 light intermediate chain 1) The protein encoded by this gene belongs to light intermediate subunit family, whose members are components of the multiprotein cytoplasmic dynein complex, which is involved in intracellular trafficking and chromosome segregation during mitosis. The protein plays a role in moving the spindle assembly checkpoint (SAC) from kinetochores to spindle poles. The protein may also mediate binding to other cargo molecules to facilitate intracellular vesicle trafficking. [provided by RefSeq, Jul 2016]

DYNC1LI1 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DYNC1LI1	NM_016141.4 link	c.607G>C	p.Asp203His	missense_variant	Exon 5 of 13	ENST00000273130.9	NP_057225.2	Q9Y6G9
DYNC1LI1	NM_001329135.2 link	c.259G>C	p.Asp87His	missense_variant	Exon 3 of 11		NP_001316064.1	E9PHI6
DYNC1LI1	XM_047448246.1 link	c.169G>C	p.Asp57His	missense_variant	Exon 4 of 12		XP_047304202.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
DYNC1LI1	ENST00000273130.9 link	c.607G>C	p.Asp203His	missense_variant	Exon 5 of 13	1	NM_016141.4	ENSP00000273130.4	Q9Y6G9
DYNC1LI1	ENST00000432458.6 link	c.259G>C	p.Asp87His	missense_variant	Exon 3 of 11	2		ENSP00000407279.2	E9PHI6
DYNC1LI1	ENST00000413350.5 link	c.454G>C	p.Asp152His	missense_variant	Exon 4 of 4	3		ENSP00000390507.1	C9JGM7
DYNC1LI1	ENST00000481915.5 link	n.530G>C		non_coding_transcript_exon_variant	Exon 5 of 11	2

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152162

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

Cov.:

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152162

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74330

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000756

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Mar 29, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.607G>C (p.D203H) alteration is located in exon 5 (coding exon 5) of the DYNC1LI1 gene. This alteration results from a G to C substitution at nucleotide position 607, causing the aspartic acid (D) at amino acid position 203 to be replaced by a histidine (H). 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

0.29

BayesDel_addAF

Benign

-0.14

BayesDel_noAF

Benign

-0.44

CADD

Pathogenic

DANN

Uncertain

0.99

DEOGEN2

Benign

0.10

T;.;T

Eigen

Uncertain

0.48

Eigen_PC

Uncertain

0.47

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.96

D;D;D

M_CAP

Benign

0.032

MetaRNN

Uncertain

0.46

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

2.0

M;.;.

PrimateAI

Benign

0.41

PROVEAN

Benign

-2.0

N;N;N

REVEL

Benign

0.28

Sift

Uncertain

0.027

D;D;D

Sift4G

Uncertain

0.036

D;D;T

Polyphen

0.92

P;P;.

Vest4

0.29

MutPred

0.66

Gain of glycosylation at P205 (P = 0.0974);.;.;

MVP

0.37

MPC

0.64

ClinPred

0.87

GERP RS

5.4

Varity_R

0.26

gMVP

0.40

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over