rs72657374

Positions:

Variant summary

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

The NM_001277115.2(DNAH11):c.9102+8G>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 0.0162 in 1,548,870 control chromosomes in the GnomAD database, including 278 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 Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.015 ( 18 hom., cov: 31)

Exomes 𝑓: 0.016 ( 260 hom. )

Consequence

DNAH11
NM_001277115.2 splice_region, intron

Scores

Splicing: ADA: 0.0001321

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:5

Conservation

PhyloP100: -0.150

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=-0.7).

BP6

Variant 7-21765597-G-A is Benign according to our data. Variant chr7-21765597-G-A is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 178729.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=1, Uncertain_significance=1, Benign=4}.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0146 (2119/144746) while in subpopulation NFE AF= 0.0186 (1232/66088). AF 95% confidence interval is 0.0178. There are 18 homozygotes in gnomad4. There are 951 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 18 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DNAH11	NM_001277115.2 linkuse as main transcript	c.9102+8G>A		splice_region_variant, intron_variant		ENST00000409508.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DNAH11	ENST00000409508.8 linkuse as main transcript	c.9102+8G>A		splice_region_variant, intron_variant		5	NM_001277115.2	P1

Frequencies

GnomAD3 genomes

AF:

0.0147

AC:

2119

AN:

144622

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0125

Gnomad AMI

AF:

0.0113

Gnomad AMR

AF:

0.0162

Gnomad ASJ

AF:

0.00789

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00432

Gnomad FIN

AF:

0.00801

Gnomad MID

AF:

0.0197

Gnomad NFE

AF:

0.0186

Gnomad OTH

AF:

0.0174

GnomAD3 exomes

AF:

0.0121

AC:

2495

AN:

205850

Hom.:

AF XY:

0.0123

AC XY:

1358

AN XY:

110820

show subpopulations

Gnomad AFR exome

AF:

0.0107

Gnomad AMR exome

AF:

0.0116

Gnomad ASJ exome

AF:

0.00970

Gnomad EAS exome

AF:

0.000126

Gnomad SAS exome

AF:

0.00526

Gnomad FIN exome

AF:

0.00932

Gnomad NFE exome

AF:

0.0168

Gnomad OTH exome

AF:

0.0177

GnomAD4 exome

AF:

0.0164

AC:

23045

AN:

1404124

Hom.:

260

Cov.:

AF XY:

0.0160

AC XY:

11141

AN XY:

695524

show subpopulations

Gnomad4 AFR exome

AF:

0.0100

Gnomad4 AMR exome

AF:

0.0119

Gnomad4 ASJ exome

AF:

0.0105

Gnomad4 EAS exome

AF:

0.0000799

Gnomad4 SAS exome

AF:

0.00593

Gnomad4 FIN exome

AF:

0.00837

Gnomad4 NFE exome

AF:

0.0185

Gnomad4 OTH exome

AF:

0.0177

GnomAD4 genome

AF:

0.0146

AC:

2119

AN:

144746

Hom.:

Cov.:

AF XY:

0.0135

AC XY:

951

AN XY:

70242

show subpopulations

Gnomad4 AFR

AF:

0.0125

Gnomad4 AMR

AF:

0.0162

Gnomad4 ASJ

AF:

0.00789

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00432

Gnomad4 FIN

AF:

0.00801

Gnomad4 NFE

AF:

0.0186

Gnomad4 OTH

AF:

0.0172

Alfa

AF:

0.0109

Hom.:

Bravo

AF:

0.0149

Asia WGS

AF:

0.00202

AC:

AN:

3476

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1Benign:5

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

Primary ciliary dyskinesia

Uncertain:1Benign:1

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -
Uncertain significance, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jun 14, 2016	- -

not specified

Benign:2

Benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	Feb 21, 2013	9102+8G>A in intron 55 of DNAH11: This variant is not expected to have clinical significance because it is not located within the conserved splice consensus seq uence. It has been identified in 1.8% (155/8422) of European American chromosome s from a broad population by the NHLBI Exome Sequencing Project (http://evs.gs.w ashington.edu/EVS; dbSNP rs72657374). -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -

Primary ciliary dyskinesia 7

Benign:1

Benign, criteria provided, single submitter

clinical testing

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Oct 03, 2023

- -

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Sep 06, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.70

CADD

Benign

2.0

DANN

Benign

0.80

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00013

dbscSNV1_RF

Benign

0.0020

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