Variant 11-103173242-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_001080463.2(DYNC2H1):c.5495C>T(p.Ser1832Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000206 in 1,599,896 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. S1832S) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000016 ( 0 hom. )

Consequence

DYNC2H1
NM_001080463.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 7.84

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 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.861

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DYNC2H1	NM_001080463.2 linkuse as main transcript	c.5495C>T	p.Ser1832Leu	missense_variant	35/90	ENST00000650373.2
DYNC2H1	NM_001377.3 linkuse as main transcript	c.5495C>T	p.Ser1832Leu	missense_variant	35/89	ENST00000375735.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DYNC2H1	ENST00000650373.2 linkuse as main transcript	c.5495C>T	p.Ser1832Leu	missense_variant	35/90		NM_001080463.2	A1	Q8NCM8-2
DYNC2H1	ENST00000375735.7 linkuse as main transcript	c.5495C>T	p.Ser1832Leu	missense_variant	35/89	1	NM_001377.3	P3	Q8NCM8-1
DYNC2H1	ENST00000334267.11 linkuse as main transcript	c.2205+38823C>T		intron_variant		1			Q8NCM8-3
DYNC2H1	ENST00000649323.1 linkuse as main transcript	c.*3040C>T		3_prime_UTR_variant, NMD_transcript_variant	33/51

Frequencies

GnomAD3 genomes

AF:

0.0000659

AC:

AN:

151814

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000169

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:

0.0000442

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000211

AC:

AN:

237074

Hom.:

AF XY:

0.0000309

AC XY:

AN XY:

129314

show subpopulations

Gnomad AFR exome

AF:

0.000141

Gnomad AMR exome

AF:

0.0000311

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:

0.0000186

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000159

AC:

AN:

1448082

Hom.:

Cov.:

AF XY:

0.0000180

AC XY:

AN XY:

720260

show subpopulations

Gnomad4 AFR exome

AF:

0.000216

Gnomad4 AMR exome

AF:

0.0000233

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000104

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000724

Gnomad4 OTH exome

AF:

0.0000167

GnomAD4 genome

AF:

0.0000659

AC:

AN:

151814

Hom.:

Cov.:

AF XY:

0.0000540

AC XY:

AN XY:

74138

show subpopulations

Gnomad4 AFR

AF:

0.000169

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:

0.0000442

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000203

Hom.:

Bravo

AF:

0.0000491

ExAC

AF:

0.0000331

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.27

BayesDel_addAF

Uncertain

0.094

BayesDel_noAF

Pathogenic

0.20

Cadd

Pathogenic

Dann

Pathogenic

1.0

DEOGEN2

Benign

0.38

T;T;.;.

Eigen

Pathogenic

0.96

Eigen_PC

Pathogenic

0.91

FATHMM_MKL

Pathogenic

0.98

M_CAP

Uncertain

0.23

MetaRNN

Pathogenic

0.86

D;D;D;D

MetaSVM

Benign

-0.30

MutationAssessor

Pathogenic

3.7

H;H;H;H

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Uncertain

0.68

PROVEAN

Pathogenic

-4.9

D;.;.;D

REVEL

Uncertain

0.64

Sift

Uncertain

0.0010

D;.;.;D

Sift4G

Uncertain

0.017

D;.;.;D

Polyphen

1.0

D;D;D;D

Vest4

0.98

MVP

0.69

MPC

0.35

ClinPred

0.96

GERP RS

5.7

Varity_R

0.76

gMVP

0.82

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over