rs1555061228

Variant summary

Our verdict is Uncertain significance. Variant got 5 ACMG points: 5P and 0B. PM2PP3_ModeratePP5

The NM_001377.3(DYNC2H1):​c.6883T>C​(p.Cys2295Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Likely pathogenic (no stars).

Frequency

Genomes: not found (cov: 32)

Consequence

DYNC2H1
NM_001377.3 missense

Scores

7
10
2

Clinical Significance

Pathogenic/Likely pathogenic no assertion criteria provided P:2

Conservation

PhyloP100: 7.36
Variant links:
Genes affected
DYNC2H1 (HGNC:2962): (dynein cytoplasmic 2 heavy chain 1) This gene encodes a large cytoplasmic dynein protein that is involved in retrograde transport in the cilium and has a role in intraflagellar transport, a process required for ciliary/flagellar assembly. Mutations in this gene cause a heterogeneous spectrum of conditions related to altered primary cilium function and often involve polydactyly, abnormal skeletogenesis, and polycystic kidneys. Alternative splicing results in multiple transcript variants encoding distinct proteins. [provided by RefSeq, Jan 2010]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 5 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.899
PP5
Variant 11-103186491-T-C is Pathogenic according to our data. Variant chr11-103186491-T-C is described in ClinVar as [Likely_pathogenic]. Clinvar id is 446552.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
DYNC2H1NM_001080463.2 linkc.6883T>C p.Cys2295Arg missense_variant 42/90 ENST00000650373.2 NP_001073932.1 Q8NCM8-2
DYNC2H1NM_001377.3 linkc.6883T>C p.Cys2295Arg missense_variant 42/89 ENST00000375735.7 NP_001368.2 Q8NCM8-1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
DYNC2H1ENST00000650373.2 linkc.6883T>C p.Cys2295Arg missense_variant 42/90 NM_001080463.2 ENSP00000497174.1 Q8NCM8-2
DYNC2H1ENST00000375735.7 linkc.6883T>C p.Cys2295Arg missense_variant 42/891 NM_001377.3 ENSP00000364887.2 Q8NCM8-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
33
GnomAD4 genome
Cov.:
32

ClinVar

Significance: Pathogenic/Likely pathogenic
Submissions summary: Pathogenic:2
Revision: no assertion criteria provided
LINK: link

Submissions by phenotype

Asphyxiating thoracic dystrophy 3 Pathogenic:2
Likely pathogenic, no assertion criteria providedresearchUniversity of Washington Center for Mendelian Genomics, University of Washington-- -
Pathogenic, no assertion criteria providedresearchDan Cohn Lab, University Of California Los AngelesJun 01, 2017- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.98
BayesDel_addAF
Pathogenic
0.25
D
BayesDel_noAF
Uncertain
0.13
CADD
Pathogenic
28
DANN
Uncertain
1.0
DEOGEN2
Uncertain
0.56
D;D;.;.
Eigen
Pathogenic
0.83
Eigen_PC
Pathogenic
0.80
FATHMM_MKL
Pathogenic
0.98
D
LIST_S2
Uncertain
0.89
.;D;.;D
M_CAP
Uncertain
0.24
D
MetaRNN
Pathogenic
0.90
D;D;D;D
MetaSVM
Benign
-0.41
T
MutationAssessor
Uncertain
2.8
M;M;M;M
PrimateAI
Uncertain
0.65
T
PROVEAN
Pathogenic
-8.8
D;.;.;D
REVEL
Uncertain
0.61
Sift
Uncertain
0.0020
D;.;.;D
Sift4G
Uncertain
0.0050
D;.;.;D
Polyphen
1.0
D;D;D;D
Vest4
0.90
MutPred
0.70
Gain of MoRF binding (P = 0.0165);Gain of MoRF binding (P = 0.0165);Gain of MoRF binding (P = 0.0165);Gain of MoRF binding (P = 0.0165);
MVP
0.74
MPC
0.50
ClinPred
0.99
D
GERP RS
5.7
Varity_R
0.99
gMVP
0.90

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: rs1555061228; hg19: chr11-103057220; API