Variant chr7-21543219-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BS1BS2

The NM_001277115.2(DNAH11):c.-27C>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0134 in 1,493,650 control chromosomes in the GnomAD database, including 148 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 0.0084 ( 7 hom., cov: 33)

Exomes 𝑓: 0.014 ( 141 hom. )

Consequence

DNAH11
NM_001277115.2 5_prime_UTR

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:1

Conservation

PhyloP100: -1.48

Variant links:

Genes affected

DNAH11 (HGNC:2942): (dynein axonemal heavy chain 11) This gene encodes a ciliary outer dynein arm protein and is a member of the dynein heavy chain family. It is a microtubule-dependent motor ATPase and has been reported to be involved in the movement of respiratory cilia. Mutations in this gene have been implicated in causing Kartagener Syndrome (a combination of situs inversus totalis and Primary Ciliary Dyskinesia (PCD), also called Immotile Cilia Syndrome 1 (ICS1)) and male sterility. [provided by RefSeq, Mar 2013]

DNAH11 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.77).

BP6

Variant 7-21543219-C-A is Benign according to our data. Variant chr7-21543219-C-A is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 359593.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=1, Uncertain_significance=1}.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0084 (1280/152318) while in subpopulation NFE AF= 0.0133 (904/68028). AF 95% confidence interval is 0.0126. There are 7 homozygotes in gnomad4. There are 584 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 7 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DNAH11	NM_001277115.2 link	c.-27C>A		5_prime_UTR_variant	1/82	ENST00000409508.8	NP_001264044.1	Q96DT5Q96NT7H9NAJ8H9NAJ7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DNAH11	ENST00000409508 link	c.-27C>A		5_prime_UTR_variant	1/82	5	NM_001277115.2	ENSP00000475939.1		Q96DT5

Frequencies

GnomAD3 genomes

AF:

0.00842

AC:

1282

AN:

152202

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00314

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0110

Gnomad ASJ

AF:

0.00547

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00662

Gnomad FIN

AF:

0.000565

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.0133

Gnomad OTH

AF:

0.00860

GnomAD3 exomes

AF:

0.00909

AC:

944

AN:

103860

Hom.:

AF XY:

0.00948

AC XY:

529

AN XY:

55820

show subpopulations

Gnomad AFR exome

AF:

0.00209

Gnomad AMR exome

AF:

0.00806

Gnomad ASJ exome

AF:

0.00806

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00548

Gnomad FIN exome

AF:

0.000881

Gnomad NFE exome

AF:

0.0152

Gnomad OTH exome

AF:

0.0134

GnomAD4 exome

AF:

0.0140

AC:

18745

AN:

1341332

Hom.:

141

Cov.:

AF XY:

0.0137

AC XY:

9007

AN XY:

657022

show subpopulations

Gnomad4 AFR exome

AF:

0.00165

Gnomad4 AMR exome

AF:

0.00989

Gnomad4 ASJ exome

AF:

0.00641

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00697

Gnomad4 FIN exome

AF:

0.00118

Gnomad4 NFE exome

AF:

0.0160

Gnomad4 OTH exome

AF:

0.0141

GnomAD4 genome

AF:

0.00840

AC:

1280

AN:

152318

Hom.:

Cov.:

AF XY:

0.00784

AC XY:

584

AN XY:

74478

show subpopulations

Gnomad4 AFR

AF:

0.00313

Gnomad4 AMR

AF:

0.0109

Gnomad4 ASJ

AF:

0.00547

Gnomad4 EAS

AF:

0.000194

Gnomad4 SAS

AF:

0.00662

Gnomad4 FIN

AF:

0.000565

Gnomad4 NFE

AF:

0.0133

Gnomad4 OTH

AF:

0.00851

Alfa

AF:

0.0105

Hom.:

Bravo

AF:

0.00956

Asia WGS

AF:

0.00260

AC:

AN:

3478

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1Benign:1

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

Primary ciliary dyskinesia

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Aug 10, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.77

CADD

Benign

5.2

DANN

Benign

0.74

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