rs368824340

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 2P and 13B. PM2BP4_StrongBP6_Very_StrongBP7

The ENST00000375735.7(DYNC2H1):ā€‹c.6918A>Gā€‹(p.Ser2306=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000149 in 1,613,010 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 Likely benign (ā˜…ā˜…). Synonymous variant affecting the same amino acid position (i.e. S2306S) has been classified as Likely benign.

Frequency

Genomes: š‘“ 0.00093 ( 1 hom., cov: 32)
Exomes š‘“: 0.000068 ( 0 hom. )

Consequence

DYNC2H1
ENST00000375735.7 synonymous

Scores

2

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: -0.129
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -11 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.57).
BP6
Variant 11-103187364-A-G is Benign according to our data. Variant chr11-103187364-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 281774.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
Synonymous conserved (PhyloP=-0.129 with no splicing effect.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
DYNC2H1NM_001080463.2 linkuse as main transcriptc.6918A>G p.Ser2306= synonymous_variant 43/90 ENST00000650373.2 NP_001073932.1
DYNC2H1NM_001377.3 linkuse as main transcriptc.6918A>G p.Ser2306= synonymous_variant 43/89 ENST00000375735.7 NP_001368.2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
DYNC2H1ENST00000650373.2 linkuse as main transcriptc.6918A>G p.Ser2306= synonymous_variant 43/90 NM_001080463.2 ENSP00000497174 A1Q8NCM8-2
DYNC2H1ENST00000375735.7 linkuse as main transcriptc.6918A>G p.Ser2306= synonymous_variant 43/891 NM_001377.3 ENSP00000364887 P3Q8NCM8-1
DYNC2H1ENST00000334267.11 linkuse as main transcriptc.2205+52945A>G intron_variant 1 ENSP00000334021 Q8NCM8-3
DYNC2H1ENST00000649323.1 linkuse as main transcriptc.*4463A>G 3_prime_UTR_variant, NMD_transcript_variant 41/51 ENSP00000497581

Frequencies

GnomAD3 genomes
AF:
0.000921
AC:
140
AN:
152044
Hom.:
1
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00328
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000197
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:
0.000478
GnomAD3 exomes
AF:
0.000189
AC:
47
AN:
248498
Hom.:
0
AF XY:
0.000119
AC XY:
16
AN XY:
134802
show subpopulations
Gnomad AFR exome
AF:
0.00278
Gnomad AMR exome
AF:
0.000116
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:
0.0000678
AC:
99
AN:
1460848
Hom.:
0
Cov.:
30
AF XY:
0.0000537
AC XY:
39
AN XY:
726700
show subpopulations
Gnomad4 AFR exome
AF:
0.00254
Gnomad4 AMR exome
AF:
0.000112
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:
9.00e-7
Gnomad4 OTH exome
AF:
0.000133
GnomAD4 genome
AF:
0.000933
AC:
142
AN:
152162
Hom.:
1
Cov.:
32
AF XY:
0.000914
AC XY:
68
AN XY:
74386
show subpopulations
Gnomad4 AFR
AF:
0.00332
Gnomad4 AMR
AF:
0.000197
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:
0.000473
Alfa
AF:
0.000499
Hom.:
0
Bravo
AF:
0.000873
Asia WGS
AF:
0.000577
AC:
2
AN:
3478

ClinVar

Significance: Benign/Likely benign
Submissions summary: Benign:6
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not specified Benign:2
Likely benign, criteria provided, single submitterclinical testingEurofins Ntd Llc (ga)Jul 28, 2015- -
Likely benign, criteria provided, single submitterclinical testingGenetic Services Laboratory, University of ChicagoMar 17, 2020- -
not provided Benign:2
Likely benign, criteria provided, single submitterclinical testingARUP Laboratories, Molecular Genetics and Genomics, ARUP LaboratoriesMar 25, 2018The c.6918A>G; p.Ser2306Ser variant (rs368824340, ClinVar variant ID 281774) does not alter the amino acid sequence of the DYNC2H1 protein and computational splice site prediction algorithms do not predict a change in the nearest splice site or creation of a cryptic splice site. This variant has not been reported in association with skeletal dysplasia in medical literature or in gene specific variation databases. This variant is listed in the genome Aggregation Database (gnomAD) with an African population frequency of 0.3% (identified on 75 out of 23,996 chromosomes). Based on the available information, the c.6918A>G variant is likely to be benign. -
Likely benign, criteria provided, single submitterclinical testingGeneDxSep 10, 2018- -
DYNC2H1-related disorder Benign:1
Likely benign, no assertion criteria providedclinical testingPreventionGenetics, part of Exact SciencesOct 12, 2020This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -
Jeune thoracic dystrophy Benign:1
Benign, criteria provided, single submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpJan 16, 2024- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.57
CADD
Benign
4.4
DANN
Benign
0.60

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.

Other links and lift over

dbSNP: rs368824340; hg19: chr11-103058093; API