rs187451323

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_ModerateBP6BP7

The NM_001377.3(DYNC2H1):c.10845G>A(p.Pro3615Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000187 in 1,608,416 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.00077 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00013 ( 1 hom. )

Consequence

DYNC2H1
NM_001377.3 synonymous

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:2B:3

Conservation

PhyloP100: -2.00

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), Ambry Genetics, Orphanet, G2P, ClinGen
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: Likely_benign. The variant received -4 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.41).

BP6

Variant 11-103283040-G-A is Benign according to our data. Variant chr11-103283040-G-A is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 302097.

BP7

Synonymous conserved (PhyloP=-2 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001377.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DYNC2H1	NM_001080463.2	MANE Plus Clinical	c.10866G>A	p.Pro3622Pro	synonymous	Exon 74 of 90	NP_001073932.1	Q8NCM8-2
	DYNC2H1	NM_001377.3	MANE Select	c.10845G>A	p.Pro3615Pro	synonymous	Exon 73 of 89	NP_001368.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
DYNC2H1	ENST00000650373.2	MANE Plus Clinical	c.10866G>A	p.Pro3622Pro	synonymous	Exon 74 of 90	ENSP00000497174.1	Q8NCM8-2
DYNC2H1	ENST00000375735.7	TSL:1 MANE Select	c.10845G>A	p.Pro3615Pro	synonymous	Exon 73 of 89	ENSP00000364887.2	Q8NCM8-1
DYNC2H1	ENST00000334267.11	TSL:1	c.2205+148621G>A		intron	N/A	ENSP00000334021.7	Q8NCM8-3

Frequencies

GnomAD3 genomes

AF:

0.000770

AC:

117

AN:

151988

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00246

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000459

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:

0.0000883

Gnomad OTH

AF:

0.000956

GnomAD2 exomes

AF:

0.000264

AC:

AN:

246644

AF XY:

0.000224

show subpopulations

Gnomad AFR exome

AF:

0.00274

Gnomad AMR exome

AF:

0.000355

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000112

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000714

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000126

AC:

183

AN:

1456308

Hom.:

Cov.:

AF XY:

0.000120

AC XY:

AN XY:

724044

show subpopulations

African (AFR)

AF:

0.00207

AC:

AN:

33386

American (AMR)

AF:

0.000451

AC:

AN:

44356

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26000

East Asian (EAS)

AF:

0.0000758

AC:

AN:

39558

South Asian (SAS)

AF:

0.0000236

AC:

AN:

84852

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53174

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5750

European-Non Finnish (NFE)

AF:

0.0000748

AC:

AN:

1109080

Other (OTH)

AF:

0.0000997

AC:

AN:

60152

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.455

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000769

AC:

117

AN:

152108

Hom.:

Cov.:

AF XY:

0.000699

AC XY:

AN XY:

74354

show subpopulations

African (AFR)

AF:

0.00246

AC:

102

AN:

41518

American (AMR)

AF:

0.000459

AC:

AN:

15264

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5186

South Asian (SAS)

AF:

0.00

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10570

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000883

AC:

AN:

67960

Other (OTH)

AF:

0.000946

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000850

Hom.:

Bravo

AF:

0.000952

ClinVar

ClinVar submissions

Significance:Conflicting classifications of pathogenicity

Revision:criteria provided, conflicting classifications

View on ClinVar

Pathogenic

VUS

Benign

Condition

Asphyxiating thoracic dystrophy 3 (2)

DYNC2H1-related disorder (1)

Jeune thoracic dystrophy (1)

Short rib-polydactyly syndrome (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.41

CADD

Benign

0.43

(source)

DANN

Benign

0.56

PhyloP100

-2.0

Mutation Taster

=100/0

polymorphism

(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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over