NM_001277115.2:c.1002T>C

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP6_Very_StrongBP7

The NM_001277115.2(DNAH11):​c.1002T>C​(p.Asp334Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000175 in 1,599,002 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000018 ( 0 hom. )

Consequence

DNAH11
NM_001277115.2 synonymous

Scores

2

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.112

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

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -13 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.53).
BP6
Variant 7-21564205-T-C is Benign according to our data. Variant chr7-21564205-T-C is described in CliVar as Likely_benign. Clinvar id is 416433.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-21564205-T-C is described in CliVar as Likely_benign. Clinvar id is 416433.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
Synonymous conserved (PhyloP=0.112 with no splicing effect.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
DNAH11NM_001277115.2 linkc.1002T>C p.Asp334Asp synonymous_variant Exon 6 of 82 ENST00000409508.8 NP_001264044.1 Q96DT5Q96NT7H9NAJ8H9NAJ7
LOC105375183XR_007060247.1 linkn.283-3965A>G intron_variant Intron 3 of 3

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
DNAH11ENST00000409508.8 linkc.1002T>C p.Asp334Asp synonymous_variant Exon 6 of 82 5 NM_001277115.2 ENSP00000475939.1 Q96DT5
DNAH11ENST00000496218.1 linkn.80+3035T>C intron_variant Intron 1 of 1 2

Frequencies

GnomAD3 genomes
AF:
0.0000132
AC:
2
AN:
151706
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
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:
0.0000294
Gnomad OTH
AF:
0.00
GnomAD2 exomes
AF:
0.0000125
AC:
3
AN:
240414
AF XY:
0.00000767
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000273
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000180
AC:
26
AN:
1447296
Hom.:
0
Cov.:
32
AF XY:
0.0000195
AC XY:
14
AN XY:
718790
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
32878
American (AMR)
AF:
0.00
AC:
0
AN:
42868
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
25640
East Asian (EAS)
AF:
0.00
AC:
0
AN:
39442
South Asian (SAS)
AF:
0.00
AC:
0
AN:
82656
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
53082
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
5706
European-Non Finnish (NFE)
AF:
0.0000226
AC:
25
AN:
1105292
Other (OTH)
AF:
0.0000167
AC:
1
AN:
59732
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.487
Heterozygous variant carriers
0
2
4
7
9
11
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Variant carriers
0
2
4
6
8
10
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
GnomAD4 genome
AF:
0.0000132
AC:
2
AN:
151706
Hom.:
0
Cov.:
32
AF XY:
0.00
AC XY:
0
AN XY:
74030
show subpopulations
⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.
African (AFR)
AF:
0.00
AC:
0
AN:
41294
American (AMR)
AF:
0.00
AC:
0
AN:
15234
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
3468
East Asian (EAS)
AF:
0.00
AC:
0
AN:
5162
South Asian (SAS)
AF:
0.00
AC:
0
AN:
4808
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
10442
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
306
European-Non Finnish (NFE)
AF:
0.0000294
AC:
2
AN:
68000
Other (OTH)
AF:
0.00
AC:
0
AN:
2080
⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.000203), which strongly suggests a high chance of mosaicism in these individuals.
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.375
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Alfa
AF:
0.0000579
Hom.:
0
Bravo
AF:
0.0000151

ClinVar

Significance: Likely benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

Primary ciliary dyskinesia Benign:2
Jul 25, 2022
Ambry Genetics
Significance:Likely benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing

This alteration is classified as likely 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 19, 2024
Labcorp Genetics (formerly Invitae), Labcorp
Significance:Likely benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.53
CADD
Benign
1.6
DANN
Benign
0.63
PhyloP100
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

Other links and lift over

dbSNP: rs370925563; hg19: chr7-21603823; API