Variant chr11-103109767-A-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 4P and 4B. PM2PM5BP4_Strong

The NM_001080463.2(DYNC2H1):c.193A>T(p.Thr65Ser) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000186 in 1,612,388 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 17/23 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. 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. T65P) has been classified as Likely pathogenic.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

DYNC2H1
NM_001080463.2 missense, splice_region

Scores

Splicing: ADA: 0.007880

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.481

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;

PM5

Other missense variant is known to change same aminoacid residue: Variant chr11-103109767-A-C is described in ClinVar as [Likely_pathogenic]. Clinvar id is 446598.Status of the report is no_assertion_criteria_provided, 0 stars.

BP4

Computational evidence support a benign effect (MetaRNN=0.043217838).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DYNC2H1	NM_001080463.2 linkuse as main transcript	c.193A>T	p.Thr65Ser	missense_variant, splice_region_variant	1/90	ENST00000650373.2
DYNC2H1	NM_001377.3 linkuse as main transcript	c.193A>T	p.Thr65Ser	missense_variant, splice_region_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.193A>T	p.Thr65Ser	missense_variant, splice_region_variant	1/90		NM_001080463.2	A1	Q8NCM8-2
DYNC2H1	ENST00000375735.7 linkuse as main transcript	c.193A>T	p.Thr65Ser	missense_variant, splice_region_variant	1/89	1	NM_001377.3	P3	Q8NCM8-1

Frequencies

GnomAD3 genomes

AF:

0.00000659

AC:

AN:

151768

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000242

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000403

AC:

AN:

247854

Hom.:

AF XY:

0.00

AC XY:

AN XY:

134440

show subpopulations

Gnomad AFR exome

AF:

0.0000646

Gnomad AMR exome

AF:

0.00

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:

0.00

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1460502

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

726434

show subpopulations

Gnomad4 AFR exome

AF:

0.0000597

Gnomad4 AMR exome

AF:

0.00

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

AF:

0.00000658

AC:

AN:

151886

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74228

show subpopulations

Gnomad4 AFR

AF:

0.0000241

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:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000151

ExAC

AF:

0.00000827

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.082

BayesDel_addAF

Benign

-0.35

BayesDel_noAF

Benign

-0.56

CADD

Benign

DANN

Benign

0.79

DEOGEN2

Benign

0.048

.;T;.;T;.;.

Eigen

Benign

-0.68

Eigen_PC

Benign

-0.54

FATHMM_MKL

Benign

0.72

LIST_S2

Benign

0.53

T;.;T;T;.;T

M_CAP

Benign

0.0092

MetaRNN

Benign

0.043

T;T;T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.4

.;L;L;L;L;L

MutationTaster

Benign

0.92

N;N;N

PrimateAI

Benign

0.32

PROVEAN

Benign

0.060

.;N;N;.;.;N

REVEL

Benign

0.050

Sift

Benign

1.0

.;T;T;.;.;T

Sift4G

Benign

0.79

.;T;T;.;.;T

Polyphen

0.0, 0.010

.;B;B;B;B;B

Vest4

0.073, 0.077, 0.089

MutPred

0.26

Gain of disorder (P = 0.039);Gain of disorder (P = 0.039);Gain of disorder (P = 0.039);Gain of disorder (P = 0.039);Gain of disorder (P = 0.039);Gain of disorder (P = 0.039);

MVP

0.21

MPC

0.057

ClinPred

0.040

GERP RS

0.83

Varity_R

0.043

gMVP

0.11

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.0079

dbscSNV1_RF

Benign

0.20

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