rs72658840

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001277115.2(DNAH11):​c.13547C>T​(p.Ala4516Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00536 in 1,601,468 control chromosomes in the GnomAD database, including 310 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/17 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.026 ( 170 hom., cov: 32)
Exomes 𝑓: 0.0032 ( 140 hom. )

Consequence

DNAH11
NM_001277115.2 missense

Scores

16

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: 2.62
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 -20 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.0014667213).
BP6
Variant 7-21901250-C-T is Benign according to our data. Variant chr7-21901250-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 226582.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-21901250-C-T is described in Lovd as [Benign].
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0862 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
DNAH11NM_001277115.2 linkuse as main transcriptc.13547C>T p.Ala4516Val missense_variant 82/82 ENST00000409508.8 NP_001264044.1
CDCA7LNM_018719.5 linkuse as main transcriptc.*1072G>A 3_prime_UTR_variant 10/10 ENST00000406877.8 NP_061189.2
CDCA7LNM_001127370.3 linkuse as main transcriptc.*1072G>A 3_prime_UTR_variant 11/11 NP_001120842.1
CDCA7LNM_001127371.3 linkuse as main transcriptc.*1072G>A 3_prime_UTR_variant 9/9 NP_001120843.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
DNAH11ENST00000409508.8 linkuse as main transcriptc.13547C>T p.Ala4516Val missense_variant 82/825 NM_001277115.2 ENSP00000475939 P1
CDCA7LENST00000406877.8 linkuse as main transcriptc.*1072G>A 3_prime_UTR_variant 10/101 NM_018719.5 ENSP00000383986 P1Q96GN5-1
CDCA7LENST00000356195.9 linkuse as main transcriptc.*1072G>A 3_prime_UTR_variant 11/112 ENSP00000348523 Q96GN5-4
CDCA7LENST00000488845.1 linkuse as main transcriptn.1594G>A non_coding_transcript_exon_variant 4/42

Frequencies

GnomAD3 genomes
AF:
0.0262
AC:
3847
AN:
146778
Hom.:
169
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0888
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00951
Gnomad ASJ
AF:
0.00180
Gnomad EAS
AF:
0.000609
Gnomad SAS
AF:
0.00193
Gnomad FIN
AF:
0.000194
Gnomad MID
AF:
0.00323
Gnomad NFE
AF:
0.000931
Gnomad OTH
AF:
0.0189
GnomAD3 exomes
AF:
0.00685
AC:
1641
AN:
239448
Hom.:
64
AF XY:
0.00522
AC XY:
677
AN XY:
129758
show subpopulations
Gnomad AFR exome
AF:
0.0867
Gnomad AMR exome
AF:
0.00476
Gnomad ASJ exome
AF:
0.00157
Gnomad EAS exome
AF:
0.000113
Gnomad SAS exome
AF:
0.000600
Gnomad FIN exome
AF:
0.000142
Gnomad NFE exome
AF:
0.000818
Gnomad OTH exome
AF:
0.00462
GnomAD4 exome
AF:
0.00325
AC:
4724
AN:
1454598
Hom.:
140
Cov.:
33
AF XY:
0.00282
AC XY:
2040
AN XY:
722758
show subpopulations
Gnomad4 AFR exome
AF:
0.0855
Gnomad4 AMR exome
AF:
0.00532
Gnomad4 ASJ exome
AF:
0.00171
Gnomad4 EAS exome
AF:
0.000355
Gnomad4 SAS exome
AF:
0.000758
Gnomad4 FIN exome
AF:
0.000226
Gnomad4 NFE exome
AF:
0.000950
Gnomad4 OTH exome
AF:
0.00719
GnomAD4 genome
AF:
0.0262
AC:
3855
AN:
146870
Hom.:
170
Cov.:
32
AF XY:
0.0247
AC XY:
1775
AN XY:
71742
show subpopulations
Gnomad4 AFR
AF:
0.0886
Gnomad4 AMR
AF:
0.00949
Gnomad4 ASJ
AF:
0.00180
Gnomad4 EAS
AF:
0.000610
Gnomad4 SAS
AF:
0.00145
Gnomad4 FIN
AF:
0.000194
Gnomad4 NFE
AF:
0.000931
Gnomad4 OTH
AF:
0.0227
Alfa
AF:
0.0141
Hom.:
30
Bravo
AF:
0.0285
TwinsUK
AF:
0.00135
AC:
5
ALSPAC
AF:
0.000519
AC:
2
ESP6500AA
AF:
0.0761
AC:
301
ESP6500EA
AF:
0.00144
AC:
12
ExAC
AF:
0.00768
AC:
928
Asia WGS
AF:
0.0240
AC:
84
AN:
3478

ClinVar

Significance: Benign/Likely benign
Submissions summary: Benign:7
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not specified Benign:2
Benign, criteria provided, single submitterclinical testingLaboratory for Molecular Medicine, Mass General Brigham Personalized MedicineFeb 21, 2013Ala4516Val in exon 82 of DNAH11: This variant is not expected to have clinical s ignificance because it has been identified in 7.6% (301/3954) of African America n chromosomes from a broad population by the NHLBI Exome Sequencing Project (htt p://evs.gs.washington.edu/EVS; dbSNP rs72658840). -
Benign, criteria provided, single submitterclinical testingPreventionGenetics, part of Exact Sciences-- -
Primary ciliary dyskinesia Benign:2
Likely benign, criteria provided, single submitterclinical testingIllumina Laboratory Services, IlluminaJun 14, 2016- -
Benign, criteria provided, single submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpJan 31, 2024- -
not provided Benign:2
Benign, criteria provided, single submitterclinical testingGeneDxFeb 17, 2021- -
Likely benign, criteria provided, single submitternot providedBreakthrough Genomics, Breakthrough Genomics-- -
Primary ciliary dyskinesia 7 Benign:1
Benign, criteria provided, single submitterclinical testingARUP Laboratories, Molecular Genetics and Genomics, ARUP LaboratoriesNov 03, 2023- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.18
BayesDel_addAF
Benign
-0.62
T
BayesDel_noAF
Benign
-0.60
CADD
Benign
15
DANN
Benign
0.97
DEOGEN2
Benign
0.012
.;.;T
Eigen
Benign
-1.1
Eigen_PC
Benign
-1.0
FATHMM_MKL
Benign
0.052
N
LIST_S2
Benign
0.79
T;T;T
MetaRNN
Benign
0.0015
T;T;T
MetaSVM
Benign
-1.0
T
MutationTaster
Benign
0.96
N;N;N
PrimateAI
Benign
0.40
T
PROVEAN
Benign
1.7
.;N;.
REVEL
Benign
0.15
Sift
Benign
0.17
.;T;.
Vest4
0.12
MVP
0.014
ClinPred
0.0098
T
GERP RS
3.8
Varity_R
0.047
gMVP
0.17

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: rs72658840; hg19: chr7-21940868; API