Variant chr11-103287549-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_Strong

The NM_001080463.2(DYNC2H1):c.11060C>A(p.Ala3687Glu) variant causes a missense change. The variant allele was found at a frequency of 0.000000686 in 1,456,872 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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A3687V) has been classified as Benign.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

DYNC2H1
NM_001080463.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 6.03

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:

(HGNC:):

links:

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ACMG classification

Classification made for transcript

Verdict is Likely_pathogenic. Variant got 6 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.974

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DYNC2H1	NM_001080463.2 linkuse as main transcript	c.11060C>A	p.Ala3687Glu	missense_variant	76/90	ENST00000650373.2	NP_001073932.1
DYNC2H1	NM_001377.3 linkuse as main transcript	c.11039C>A	p.Ala3680Glu	missense_variant	75/89	ENST00000375735.7	NP_001368.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DYNC2H1	ENST00000650373.2 linkuse as main transcript	c.11060C>A	p.Ala3687Glu	missense_variant	76/90		NM_001080463.2	ENSP00000497174	A1	Q8NCM8-2
DYNC2H1	ENST00000375735.7 linkuse as main transcript	c.11039C>A	p.Ala3680Glu	missense_variant	75/89	1	NM_001377.3	ENSP00000364887	P3	Q8NCM8-1
	ENST00000649070.1 linkuse as main transcript	n.690+5467G>T		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000410

AC:

AN:

244088

Hom.:

AF XY:

0.00000755

AC XY:

AN XY:

132410

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000338

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

6.86e-7

AC:

AN:

1456872

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

724510

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000118

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.97

BayesDel_addAF

Uncertain

0.15

BayesDel_noAF

Uncertain

0.070

CADD

Pathogenic

DANN

Uncertain

0.99

DEOGEN2

Benign

0.41

T;T;.;.

Eigen

Pathogenic

0.86

Eigen_PC

Pathogenic

0.83

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Uncertain

0.91

.;D;.;D

M_CAP

Benign

0.054

MetaRNN

Pathogenic

0.97

D;D;D;D

MetaSVM

Benign

-1.0

MutationAssessor

Pathogenic

3.0

M;M;.;.

MutationTaster

Benign

8.0e-9

P;P;P

PrimateAI

Uncertain

0.66

PROVEAN

Uncertain

-4.3

D;.;.;D

REVEL

Uncertain

0.49

Sift

Uncertain

0.0020

D;.;.;D

Sift4G

Uncertain

0.0050

D;.;.;D

Polyphen

0.96

D;D;D;D

Vest4

0.80

MutPred

0.84

Gain of helix (P = 0.132);Gain of helix (P = 0.132);.;.;

MVP

0.61

MPC

0.30

ClinPred

0.99

GERP RS

5.8

Varity_R

0.94

gMVP

0.80

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