11-103399879-G-A

Position:

chr11-103399879-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001080463.2(DYNC2H1):c.12387+7G>A variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.471 in 1,605,638 control chromosomes in the GnomAD database, including 180,693 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.51 ( 20164 hom., cov: 32)

Exomes 𝑓: 0.47 ( 160529 hom. )

Consequence

DYNC2H1
NM_001080463.2 splice_region, intron

Scores

Splicing: ADA: 0.00002362

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:10

Conservation

PhyloP100: -1.20

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.87).

BP6

Variant 11-103399879-G-A is Benign according to our data. Variant chr11-103399879-G-A is described in ClinVar as [Benign]. Clinvar id is 302120.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-103399879-G-A is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.61 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DYNC2H1	NM_001080463.2 linkuse as main transcript	c.12387+7G>A		splice_region_variant, intron_variant		ENST00000650373.2	NP_001073932.1
DYNC2H1	NM_001377.3 linkuse as main transcript	c.12366+7G>A		splice_region_variant, intron_variant		ENST00000375735.7	NP_001368.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DYNC2H1	ENST00000375735.7 linkuse as main transcript	c.12366+7G>A		splice_region_variant, intron_variant		1	NM_001377.3	ENSP00000364887	P3	Q8NCM8-1
DYNC2H1	ENST00000650373.2 linkuse as main transcript	c.12387+7G>A		splice_region_variant, intron_variant			NM_001080463.2	ENSP00000497174	A1	Q8NCM8-2

Frequencies

GnomAD3 genomes

AF:

0.511

AC:

77607

AN:

151962

Hom.:

20131

Cov.:

show subpopulations

Gnomad AFR

AF:

0.617

Gnomad AMI

AF:

0.398

Gnomad AMR

AF:

0.536

Gnomad ASJ

AF:

0.455

Gnomad EAS

AF:

0.529

Gnomad SAS

AF:

0.547

Gnomad FIN

AF:

0.432

Gnomad MID

AF:

0.528

Gnomad NFE

AF:

0.454

Gnomad OTH

AF:

0.495

GnomAD3 exomes

AF:

0.490

AC:

121112

AN:

247116

Hom.:

30362

AF XY:

0.487

AC XY:

65276

AN XY:

134030

show subpopulations

Gnomad AFR exome

AF:

0.620

Gnomad AMR exome

AF:

0.560

Gnomad ASJ exome

AF:

0.450

Gnomad EAS exome

AF:

0.535

Gnomad SAS exome

AF:

0.552

Gnomad FIN exome

AF:

0.417

Gnomad NFE exome

AF:

0.445

Gnomad OTH exome

AF:

0.471

GnomAD4 exome

AF:

0.467

AC:

678353

AN:

1453558

Hom.:

160529

Cov.:

AF XY:

0.469

AC XY:

339169

AN XY:

723522

show subpopulations

Gnomad4 AFR exome

AF:

0.629

Gnomad4 AMR exome

AF:

0.552

Gnomad4 ASJ exome

AF:

0.455

Gnomad4 EAS exome

AF:

0.564

Gnomad4 SAS exome

AF:

0.554

Gnomad4 FIN exome

AF:

0.414

Gnomad4 NFE exome

AF:

0.450

Gnomad4 OTH exome

AF:

0.481

GnomAD4 genome

AF:

0.511

AC:

77688

AN:

152080

Hom.:

20164

Cov.:

AF XY:

0.514

AC XY:

38212

AN XY:

74324

show subpopulations

Gnomad4 AFR

AF:

0.617

Gnomad4 AMR

AF:

0.537

Gnomad4 ASJ

AF:

0.455

Gnomad4 EAS

AF:

0.529

Gnomad4 SAS

AF:

0.545

Gnomad4 FIN

AF:

0.432

Gnomad4 NFE

AF:

0.454

Gnomad4 OTH

AF:

0.495

Alfa

AF:

0.467

Hom.:

5423

Bravo

AF:

0.518

Asia WGS

AF:

0.567

AC:

1973

AN:

3476

EpiCase

AF:

0.447

EpiControl

AF:

0.441

ClinVar

Significance: Benign

Submissions summary: Benign:10

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:5

Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 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	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -
Benign, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -
Benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	Mar 28, 2016	Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency -

Asphyxiating thoracic dystrophy 3

Benign:2

Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Jul 30, 2021	- -
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. -

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

- -

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

-0.87

CADD

Benign

0.32

DANN

Benign

0.67

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000024

dbscSNV1_RF

Benign

0.0040

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