7-21789325-A-G

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2BP4_StrongBP6

The NM_001277115.2(DNAH11):​c.10009A>G​(p.Ile3337Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000494 in 1,417,256 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: not found (cov: 31)
Exomes š‘“: 0.0000049 ( 0 hom. )

Consequence

DNAH11
NM_001277115.2 missense

Scores

17

Clinical Significance

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

Conservation

PhyloP100: 1.25
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -3 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.03841403).
BP6
Variant 7-21789325-A-G is Benign according to our data. Variant chr7-21789325-A-G is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 2440912.We mark this variant Likely_benign, oryginal submissions are: {Benign=1, Uncertain_significance=1}.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
DNAH11NM_001277115.2 linkc.10009A>G p.Ile3337Val missense_variant Exon 61 of 82 ENST00000409508.8 NP_001264044.1 Q96DT5Q96NT7H9NAJ8H9NAJ7

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
DNAH11ENST00000409508.8 linkc.10009A>G p.Ile3337Val missense_variant Exon 61 of 82 5 NM_001277115.2 ENSP00000475939.1 Q96DT5

Frequencies

GnomAD3 genomes
Cov.:
31
GnomAD3 exomes
AF:
0.0000332
AC:
6
AN:
180692
Hom.:
0
AF XY:
0.0000314
AC XY:
3
AN XY:
95616
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000748
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000428
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000396
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000494
AC:
7
AN:
1417256
Hom.:
0
Cov.:
30
AF XY:
0.00000285
AC XY:
2
AN XY:
700606
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000525
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000250
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000184
Gnomad4 OTH exome
AF:
0.0000170
GnomAD4 genome
Cov.:
31
Alfa
AF:
0.0000712
Hom.:
0
Bravo
AF:
0.0000113
ExAC
AF:
0.00000843
AC:
1

ClinVar

Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:1Benign:1
Revision: criteria provided, conflicting classifications
LINK: link

Submissions by phenotype

Primary ciliary dyskinesia 7 Uncertain:1
Nov 18, 2021
Revvity Omics, Revvity
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

- -

Primary ciliary dyskinesia Benign:1
Feb 23, 2024
Labcorp Genetics (formerly Invitae), Labcorp
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.086
BayesDel_addAF
Benign
-0.28
T
BayesDel_noAF
Benign
-0.44
CADD
Benign
14
DANN
Benign
0.97
DEOGEN2
Benign
0.18
.;.;T
Eigen
Benign
-0.77
Eigen_PC
Benign
-0.71
FATHMM_MKL
Benign
0.47
N
LIST_S2
Benign
0.72
T;T;T
M_CAP
Benign
0.018
T
MetaRNN
Benign
0.038
T;T;T
MetaSVM
Benign
-0.93
T
PrimateAI
Benign
0.33
T
PROVEAN
Benign
-0.80
.;N;.
REVEL
Benign
0.16
Sift
Benign
0.12
.;T;.
Vest4
0.29
MVP
0.33
ClinPred
0.040
T
GERP RS
1.1
Varity_R
0.072
gMVP
0.11

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.

Other links and lift over

dbSNP: rs145645790; hg19: chr7-21828943; API