Genetic Variant DNAH11:c.3766-10C>G (chr7-21606637-C-G) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001277115.2(DNAH11):c.3766-10C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000029 ( 0 hom., cov: 16)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

DNAH11
NM_001277115.2 intron

Scores

Splicing: ADA: 0.0002925

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.752

Publications

0 publications found

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 Gene-Disease associations (from GenCC):

primary ciliary dyskinesia 7
Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: PanelApp Australia, Laboratory for Molecular Medicine, Labcorp Genetics (formerly Invitae), ClinGen
primary ciliary dyskinesia
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

DNAH11 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNAH11	NM_001277115.2 link	c.3766-10C>G		intron_variant	Intron 19 of 81	ENST00000409508.8	NP_001264044.1	Q96DT5Q96NT7H9NAJ8H9NAJ7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DNAH11	ENST00000409508.8 link	c.3766-10C>G		intron_variant	Intron 19 of 81	5	NM_001277115.2	ENSP00000475939.1		Q96DT5

Frequencies

GnomAD3 genomes

AF:

0.0000294

AC:

AN:

68008

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000607

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000287

Gnomad OTH

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

749662

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

377646

African (AFR)

AF:

0.00

AC:

AN:

17810

American (AMR)

AF:

0.00

AC:

AN:

18522

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

14984

East Asian (EAS)

AF:

0.00

AC:

AN:

26470

South Asian (SAS)

AF:

0.00

AC:

AN:

48000

European-Finnish (FIN)

AF:

0.00

AC:

AN:

32518

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2594

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

554316

Other (OTH)

AF:

0.00

AC:

AN:

34448

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000294

AC:

AN:

68050

Hom.:

Cov.:

AF XY:

0.0000629

AC XY:

AN XY:

31792

show subpopulations

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.0000605

AC:

AN:

16536

American (AMR)

AF:

0.00

AC:

AN:

5980

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2016

East Asian (EAS)

AF:

0.00

AC:

AN:

1936

South Asian (SAS)

AF:

0.00

AC:

AN:

2362

European-Finnish (FIN)

AF:

0.00

AC:

AN:

2938

Middle Eastern (MID)

AF:

0.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.0000287

AC:

AN:

34880

Other (OTH)

AF:

0.00

AC:

AN:

850

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.225

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

0.046

(source)

DANN

Benign

0.26

PhyloP100

-0.75

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00029

dbscSNV1_RF

Benign

0.026

SpliceAI score (max)

0.15

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over