Variant chr11-103109638-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP6_Moderate

The NM_001080463.2(DYNC2H1):c.64G>C(p.Gly22Arg) variant causes a missense change. The variant allele was found at a frequency of 0.00000479 in 1,461,688 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely benign (★). Synonymous variant affecting the same amino acid position (i.e. G22G) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000048 ( 0 hom. )

Consequence

DYNC2H1
NM_001080463.2 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 6.41

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 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP6

Variant 11-103109638-G-C is Benign according to our data. Variant chr11-103109638-G-C is described in ClinVar as [Likely_benign]. Clinvar id is 698370.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DYNC2H1	NM_001080463.2 linkuse as main transcript	c.64G>C	p.Gly22Arg	missense_variant	1/90	ENST00000650373.2
DYNC2H1	NM_001377.3 linkuse as main transcript	c.64G>C	p.Gly22Arg	missense_variant	1/89	ENST00000375735.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DYNC2H1	ENST00000650373.2 linkuse as main transcript	c.64G>C	p.Gly22Arg	missense_variant	1/90		NM_001080463.2	A1	Q8NCM8-2
DYNC2H1	ENST00000375735.7 linkuse as main transcript	c.64G>C	p.Gly22Arg	missense_variant	1/89	1	NM_001377.3	P3	Q8NCM8-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000281

AC:

AN:

249114

Hom.:

AF XY:

0.0000148

AC XY:

AN XY:

135160

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000145

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:

0.00

Gnomad OTH exome

AF:

0.000331

GnomAD4 exome

AF:

0.00000479

AC:

AN:

1461688

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

727130

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000157

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.0000151

ExAC

AF:

0.0000165

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Jeune thoracic dystrophy

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Invitae

Jan 11, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.45

BayesDel_addAF

Uncertain

0.056

BayesDel_noAF

Uncertain

0.10

CADD

Uncertain

DANN

Pathogenic

1.0

DEOGEN2

Uncertain

0.49

.;T;.;T;.;.

Eigen

Pathogenic

0.77

Eigen_PC

Pathogenic

0.74

FATHMM_MKL

Uncertain

0.94

LIST_S2

Uncertain

0.89

D;.;D;D;.;D

M_CAP

Benign

0.055

MetaRNN

Uncertain

0.69

D;D;D;D;D;D

MetaSVM

Benign

-0.77

MutationAssessor

Uncertain

2.3

.;M;M;M;M;M

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Uncertain

0.64

PROVEAN

Uncertain

-3.6

.;D;D;.;.;D

REVEL

Uncertain

0.41

Sift

Pathogenic

0.0

.;D;D;.;.;D

Sift4G

Uncertain

0.026

.;D;D;.;.;D

Polyphen

0.99, 1.0, 1.0

.;D;D;D;D;D

Vest4

0.76, 0.87, 0.78

MutPred

0.58

Gain of solvent accessibility (P = 0.006);Gain of solvent accessibility (P = 0.006);Gain of solvent accessibility (P = 0.006);Gain of solvent accessibility (P = 0.006);Gain of solvent accessibility (P = 0.006);Gain of solvent accessibility (P = 0.006);

MVP

0.60

MPC

0.17

ClinPred

0.88

GERP RS

5.5

Varity_R

0.69

gMVP

0.74

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