rs775630937

Variant names:

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001080463.2(DYNC2H1):c.10895C>T(p.Ala3632Val) variant causes a missense change. The variant allele was found at a frequency of 0.00000206 in 1,454,628 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★). Synonymous variant affecting the same amino acid position (i.e. A3632A) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

DYNC2H1
NM_001080463.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.79

Publications

0 publications found

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]

DYNC2H1 Gene-Disease associations (from GenCC):

asphyxiating thoracic dystrophy 3
Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), G2P, Orphanet, Ambry Genetics
Jeune syndrome
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
short rib-polydactyly syndrome, Majewski type
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
short rib-polydactyly syndrome, Verma-Naumoff type
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

DYNC2H1 links:

ENSG00000285878 (HGNC:):

ENSG00000285878 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 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
DYNC2H1	NM_001080463.2 link	c.10895C>T	p.Ala3632Val	missense_variant	Exon 74 of 90	ENST00000650373.2	NP_001073932.1	Q8NCM8-2
DYNC2H1	NM_001377.3 link	c.10874C>T	p.Ala3625Val	missense_variant	Exon 73 of 89	ENST00000375735.7	NP_001368.2	Q8NCM8-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DYNC2H1	ENST00000650373.2 link	c.10895C>T	p.Ala3632Val	missense_variant	Exon 74 of 90		NM_001080463.2	ENSP00000497174.1		Q8NCM8-2
DYNC2H1	ENST00000375735.7 link	c.10874C>T	p.Ala3625Val	missense_variant	Exon 73 of 89	1	NM_001377.3	ENSP00000364887.2		Q8NCM8-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000812

AC:

AN:

246194

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000592

Gnomad ASJ exome

AF:

0.00

Gnomad EAS 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:

0.00000206

AC:

AN:

1454628

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

723142

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33370

American (AMR)

AF:

0.0000677

AC:

AN:

44284

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25940

East Asian (EAS)

AF:

0.00

AC:

AN:

39506

South Asian (SAS)

AF:

0.00

AC:

AN:

84792

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53098

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5750

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1107808

Other (OTH)

AF:

0.00

AC:

AN:

60080

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ExAC

AF:

0.0000248

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Uncertain:1

Jan 21, 2016

Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.27

BayesDel_addAF

Uncertain

0.042

BayesDel_noAF

Benign

-0.18

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.12

T;T;.;.

Eigen

Uncertain

0.56

Eigen_PC

Uncertain

0.57

FATHMM_MKL

Uncertain

0.95

LIST_S2

Uncertain

0.90

.;D;.;D

M_CAP

Benign

0.025

MetaRNN

Uncertain

0.46

T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.7

M;M;.;.

PhyloP100

3.8

PrimateAI

Uncertain

0.64

PROVEAN

Benign

-2.3

N;.;.;N

REVEL

Benign

0.25

Sift

Benign

0.064

T;.;.;T

Sift4G

Benign

0.22

T;.;.;T

Polyphen

0.90

P;P;P;P

Vest4

0.78

MutPred

0.63

Gain of ubiquitination at K3630 (P = 0.1985);Gain of ubiquitination at K3630 (P = 0.1985);.;.;

MVP

0.64

MPC

0.26

ClinPred

0.86

GERP RS

5.4

Varity_R

0.36

gMVP

0.50

Mutation Taster

=33/67

disease causing

(source)

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

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rs775630937

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over