rs200609513

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2

The NM_001277115.2(DNAH11):​c.13399G>A​(p.Val4467Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000351 in 1,613,578 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/18 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: 𝑓 0.00031 ( 0 hom., cov: 33)
Exomes 𝑓: 0.00036 ( 2 hom. )

Consequence

DNAH11
NM_001277115.2 missense

Scores

17

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:3

Conservation

PhyloP100: -0.994
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]
CDCA7L (HGNC:30777): (cell division cycle associated 7 like) Acts upstream of or within positive regulation of cell population proliferation. Located in cytosol; fibrillar center; and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -9 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.0067833364).
BP6
Variant 7-21901102-G-A is Benign according to our data. Variant chr7-21901102-G-A is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 359699.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=1, Uncertain_significance=1, Benign=1}.
BS2
High Homozygotes in GnomAdExome4 at 2 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
DNAH11NM_001277115.2 linkc.13399G>A p.Val4467Met missense_variant Exon 82 of 82 ENST00000409508.8 NP_001264044.1 Q96DT5Q96NT7H9NAJ8H9NAJ7
CDCA7LNM_018719.5 linkc.*1220C>T 3_prime_UTR_variant Exon 10 of 10 ENST00000406877.8 NP_061189.2 Q96GN5-1A0A024RA51A8K8X5
CDCA7LNM_001127370.3 linkc.*1220C>T 3_prime_UTR_variant Exon 11 of 11 NP_001120842.1 Q96GN5-4
CDCA7LNM_001127371.3 linkc.*1220C>T 3_prime_UTR_variant Exon 9 of 9 NP_001120843.1 Q96GN5-5

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
DNAH11ENST00000409508.8 linkc.13399G>A p.Val4467Met missense_variant Exon 82 of 82 5 NM_001277115.2 ENSP00000475939.1 Q96DT5
CDCA7LENST00000406877 linkc.*1220C>T 3_prime_UTR_variant Exon 10 of 10 1 NM_018719.5 ENSP00000383986.3 Q96GN5-1

Frequencies

GnomAD3 genomes
AF:
0.000316
AC:
48
AN:
152022
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.0000965
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000131
Gnomad ASJ
AF:
0.000289
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00352
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00633
Gnomad NFE
AF:
0.000309
Gnomad OTH
AF:
0.000480
GnomAD3 exomes
AF:
0.000550
AC:
137
AN:
249018
Hom.:
0
AF XY:
0.000703
AC XY:
95
AN XY:
135150
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.000290
Gnomad ASJ exome
AF:
0.0000994
Gnomad EAS exome
AF:
0.0000556
Gnomad SAS exome
AF:
0.00203
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000523
Gnomad OTH exome
AF:
0.000661
GnomAD4 exome
AF:
0.000356
AC:
520
AN:
1461438
Hom.:
2
Cov.:
33
AF XY:
0.000432
AC XY:
314
AN XY:
727006
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.000425
Gnomad4 ASJ exome
AF:
0.000230
Gnomad4 EAS exome
AF:
0.000101
Gnomad4 SAS exome
AF:
0.00190
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.000240
Gnomad4 OTH exome
AF:
0.000646
GnomAD4 genome
AF:
0.000309
AC:
47
AN:
152140
Hom.:
0
Cov.:
33
AF XY:
0.000296
AC XY:
22
AN XY:
74370
show subpopulations
Gnomad4 AFR
AF:
0.0000963
Gnomad4 AMR
AF:
0.000131
Gnomad4 ASJ
AF:
0.000289
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00332
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000309
Gnomad4 OTH
AF:
0.000475
Alfa
AF:
0.000377
Hom.:
0
Bravo
AF:
0.000253
TwinsUK
AF:
0.000270
AC:
1
ALSPAC
AF:
0.000259
AC:
1
ESP6500AA
AF:
0.00
AC:
0
ESP6500EA
AF:
0.000729
AC:
6
ExAC
AF:
0.000621
AC:
75
Asia WGS
AF:
0.000866
AC:
3
AN:
3478
EpiCase
AF:
0.000654
EpiControl
AF:
0.000593

ClinVar

Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:1Benign:3
Revision: criteria provided, conflicting classifications
LINK: link

Submissions by phenotype

Primary ciliary dyskinesia Uncertain:1Benign:2
Jun 06, 2024
Ambry Genetics
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Jun 14, 2016
Illumina Laboratory Services, Illumina
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

- -

Dec 13, 2024
Labcorp Genetics (formerly Invitae), Labcorp
Significance: Likely benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

- -

DNAH11-related disorder Benign:1
Jan 18, 2023
PreventionGenetics, part of Exact Sciences
Significance: Likely benign
Review Status: no assertion criteria provided
Collection Method: clinical testing

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.084
BayesDel_addAF
Benign
-0.62
T
BayesDel_noAF
Benign
-0.67
CADD
Benign
0.072
DANN
Benign
0.97
DEOGEN2
Benign
0.056
.;.;T
Eigen
Benign
-0.97
Eigen_PC
Benign
-1.1
FATHMM_MKL
Benign
0.072
N
LIST_S2
Benign
0.48
T;T;T
M_CAP
Benign
0.012
T
MetaRNN
Benign
0.0068
T;T;T
MetaSVM
Benign
-1.0
T
PrimateAI
Benign
0.23
T
PROVEAN
Benign
-2.0
.;N;.
REVEL
Benign
0.067
Sift
Benign
0.094
.;T;.
Vest4
0.14
MVP
0.067
ClinPred
0.048
T
GERP RS
-4.5
Varity_R
0.041
gMVP
0.16

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: rs200609513; hg19: chr7-21940720; COSMIC: COSV100176122; COSMIC: COSV100176122; API