Variant chr11-103109481-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_001080463.2(DYNC2H1):c.-94G>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0028 in 1,287,182 control chromosomes in the GnomAD database, including 86 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.013 ( 50 hom., cov: 32)

Exomes 𝑓: 0.0014 ( 36 hom. )

Consequence

DYNC2H1
NM_001080463.2 5_prime_UTR

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.0900

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 Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.85).

BP6

Variant 11-103109481-G-T is Benign according to our data. Variant chr11-103109481-G-T is described in ClinVar as [Likely_benign]. Clinvar id is 301993.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0134 (2045/152318) while in subpopulation AFR AF= 0.0456 (1894/41566). AF 95% confidence interval is 0.0439. There are 50 homozygotes in gnomad4. There are 928 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 50 AR,Digenic gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DYNC2H1	NM_001080463.2 linkuse as main transcript	c.-94G>T		5_prime_UTR_variant	1/90	ENST00000650373.2
DYNC2H1	NM_001377.3 linkuse as main transcript	c.-94G>T		5_prime_UTR_variant	1/89	ENST00000375735.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DYNC2H1	ENST00000375735.7 linkuse as main transcript	c.-94G>T		5_prime_UTR_variant	1/89	1	NM_001377.3	P3	Q8NCM8-1
DYNC2H1	ENST00000650373.2 linkuse as main transcript	c.-94G>T		5_prime_UTR_variant	1/90		NM_001080463.2	A1	Q8NCM8-2

Frequencies

GnomAD3 genomes

AF:

0.0134

AC:

2043

AN:

152200

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0457

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00746

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000323

Gnomad OTH

AF:

0.00669

GnomAD4 exome

AF:

0.00138

AC:

1565

AN:

1134864

Hom.:

Cov.:

AF XY:

0.00126

AC XY:

705

AN XY:

561422

show subpopulations

Gnomad4 AFR exome

AF:

0.0436

Gnomad4 AMR exome

AF:

0.00266

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000934

Gnomad4 FIN exome

AF:

0.000125

Gnomad4 NFE exome

AF:

0.000187

Gnomad4 OTH exome

AF:

0.00305

GnomAD4 genome

AF:

0.0134

AC:

2045

AN:

152318

Hom.:

Cov.:

AF XY:

0.0125

AC XY:

928

AN XY:

74478

show subpopulations

Gnomad4 AFR

AF:

0.0456

Gnomad4 AMR

AF:

0.00745

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000323

Gnomad4 OTH

AF:

0.00662

Alfa

AF:

0.00625

Hom.:

Bravo

AF:

0.0152

Asia WGS

AF:

0.00231

AC:

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 26, 2018

- -

Jeune thoracic dystrophy

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

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. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

4.6

DANN

Benign

0.63

Splicing

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