11-103253406-T-G

Position:

chr11-103253406-T-G

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_001080463.2(DYNC2H1):c.10185T>G(p.Thr3395=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.13 in 1,612,672 control chromosomes in the GnomAD database, including 15,438 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Synonymous variant affecting the same amino acid position (i.e. T3395T) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.18 ( 3005 hom., cov: 32)

Exomes 𝑓: 0.12 ( 12433 hom. )

Consequence

DYNC2H1
NM_001080463.2 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: 0.0130

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.45).

BP6

Variant 11-103253406-T-G is Benign according to our data. Variant chr11-103253406-T-G is described in ClinVar as [Benign]. Clinvar id is 302088.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-103253406-T-G is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=0.013 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.317 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DYNC2H1	NM_001080463.2 linkuse as main transcript	c.10185T>G	p.Thr3395=	synonymous_variant	67/90	ENST00000650373.2
DYNC2H1	NM_001377.3 linkuse as main transcript	c.10164T>G	p.Thr3388=	synonymous_variant	66/89	ENST00000375735.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DYNC2H1	ENST00000650373.2 linkuse as main transcript	c.10185T>G	p.Thr3395=	synonymous_variant	67/90		NM_001080463.2	A1	Q8NCM8-2
DYNC2H1	ENST00000375735.7 linkuse as main transcript	c.10164T>G	p.Thr3388=	synonymous_variant	66/89	1	NM_001377.3	P3	Q8NCM8-1
DYNC2H1	ENST00000334267.11 linkuse as main transcript	c.2205+118987T>G		intron_variant		1			Q8NCM8-3
	ENST00000649070.1 linkuse as main transcript	n.691-1102A>C		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes

AF:

0.176

AC:

26741

AN:

151912

Hom.:

2998

Cov.:

show subpopulations

Gnomad AFR

AF:

0.321

Gnomad AMI

AF:

0.0735

Gnomad AMR

AF:

0.103

Gnomad ASJ

AF:

0.0638

Gnomad EAS

AF:

0.0971

Gnomad SAS

AF:

0.109

Gnomad FIN

AF:

0.187

Gnomad MID

AF:

0.0665

Gnomad NFE

AF:

0.122

Gnomad OTH

AF:

0.149

GnomAD3 exomes

AF:

0.128

AC:

31805

AN:

248772

Hom.:

2459

AF XY:

0.123

AC XY:

16618

AN XY:

134962

show subpopulations

Gnomad AFR exome

AF:

0.328

Gnomad AMR exome

AF:

0.100

Gnomad ASJ exome

AF:

0.0656

Gnomad EAS exome

AF:

0.0985

Gnomad SAS exome

AF:

0.111

Gnomad FIN exome

AF:

0.173

Gnomad NFE exome

AF:

0.116

Gnomad OTH exome

AF:

0.111

GnomAD4 exome

AF:

0.125

AC:

182198

AN:

1460640

Hom.:

12433

Cov.:

AF XY:

0.123

AC XY:

89639

AN XY:

726628

show subpopulations

Gnomad4 AFR exome

AF:

0.328

Gnomad4 AMR exome

AF:

0.103

Gnomad4 ASJ exome

AF:

0.0622

Gnomad4 EAS exome

AF:

0.122

Gnomad4 SAS exome

AF:

0.111

Gnomad4 FIN exome

AF:

0.167

Gnomad4 NFE exome

AF:

0.120

Gnomad4 OTH exome

AF:

0.131

GnomAD4 genome

AF:

0.176

AC:

26776

AN:

152032

Hom.:

3005

Cov.:

AF XY:

0.175

AC XY:

13037

AN XY:

74318

show subpopulations

Gnomad4 AFR

AF:

0.321

Gnomad4 AMR

AF:

0.103

Gnomad4 ASJ

AF:

0.0638

Gnomad4 EAS

AF:

0.0971

Gnomad4 SAS

AF:

0.107

Gnomad4 FIN

AF:

0.187

Gnomad4 NFE

AF:

0.121

Gnomad4 OTH

AF:

0.149

Alfa

AF:

0.118

Hom.:

1813

Bravo

AF:

0.176

Asia WGS

AF:

0.115

AC:

398

AN:

3474

EpiCase

AF:

0.110

EpiControl

AF:

0.102

ClinVar

Significance: Benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:4

Benign, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -
Benign, no assertion criteria provided	clinical testing	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 29, 2016	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -
Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Jeune thoracic dystrophy

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Feb 01, 2024

- -

Asphyxiating thoracic dystrophy 3

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Short rib-polydactyly syndrome

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.45

CADD

Benign

6.6

DANN

Benign

0.66

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