chr7-21901250-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -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. 14/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Synonymous variant affecting the same amino acid position (i.e. A4516A) has been classified 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

Clinical Significance

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

Conservation

PhyloP100: 2.62

Publications

2 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 links:

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]

CDCA7L links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 Benign/Likely_benign. ClinVar VariationId is 226582.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0862 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001277115.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
DNAH11	NM_001277115.2	MANE Select	c.13547C>T	p.Ala4516Val	missense	Exon 82 of 82	NP_001264044.1
CDCA7L	NM_018719.5	MANE Select	c.*1072G>A		3_prime_UTR	Exon 10 of 10	NP_061189.2
CDCA7L	NM_001127370.3		c.*1072G>A		3_prime_UTR	Exon 11 of 11	NP_001120842.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
DNAH11	ENST00000409508.8	TSL:5 MANE Select	c.13547C>T	p.Ala4516Val	missense	Exon 82 of 82	ENSP00000475939.1
CDCA7L	ENST00000406877.8	TSL:1 MANE Select	c.*1072G>A		3_prime_UTR	Exon 10 of 10	ENSP00000383986.3
CDCA7L	ENST00000488845.1	TSL:2	n.1594G>A		non_coding_transcript_exon	Exon 4 of 4

Frequencies

GnomAD3 genomes

AF:

0.0262

AC:

3847

AN:

146778

Hom.:

169

Cov.:

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

GnomAD2 exomes

AF:

0.00685

AC:

1641

AN:

239448

AF XY:

0.00522

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 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.:

AF XY:

0.00282

AC XY:

2040

AN XY:

722758

show subpopulations

African (AFR)

AF:

0.0855

AC:

2845

AN:

33268

American (AMR)

AF:

0.00532

AC:

236

AN:

44348

Ashkenazi Jewish (ASJ)

AF:

0.00171

AC:

AN:

25768

East Asian (EAS)

AF:

0.000355

AC:

AN:

39458

South Asian (SAS)

AF:

0.000758

AC:

AN:

84428

European-Finnish (FIN)

AF:

0.000226

AC:

AN:

53202

Middle Eastern (MID)

AF:

0.00418

AC:

AN:

5740

European-Non Finnish (NFE)

AF:

0.000950

AC:

1053

AN:

1108328

Other (OTH)

AF:

0.00719

AC:

432

AN:

60058

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.484

Heterozygous variant carriers

238

476

715

953

1191

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

116

232

348

464

580

<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:

0.0262

AC:

3855

AN:

146870

Hom.:

170

Cov.:

AF XY:

0.0247

AC XY:

1775

AN XY:

71742

show subpopulations

African (AFR)

AF:

0.0886

AC:

3587

AN:

40478

American (AMR)

AF:

0.00949

AC:

143

AN:

15064

Ashkenazi Jewish (ASJ)

AF:

0.00180

AC:

AN:

3326

East Asian (EAS)

AF:

0.000610

AC:

AN:

4918

South Asian (SAS)

AF:

0.00145

AC:

AN:

4138

European-Finnish (FIN)

AF:

0.000194

AC:

AN:

10332

Middle Eastern (MID)

AF:

0.00345

AC:

AN:

290

European-Non Finnish (NFE)

AF:

0.000931

AC:

AN:

65530

Other (OTH)

AF:

0.0227

AC:

AN:

2026

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

184

368

552

736

920

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

108

144

180

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0218

Hom.:

103

Bravo

AF:

0.0285

TwinsUK

AF:

0.00135

AC:

ALSPAC

AF:

0.000519

AC:

ESP6500AA

AF:

0.0761

AC:

301

ESP6500EA

AF:

0.00144

AC:

ExAC

AF:

0.00768

AC:

928

Asia WGS

AF:

0.0240

AC:

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

Feb 21, 2013

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Ala4516Val 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).

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Primary ciliary dyskinesia

Benign:2

Jan 29, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:not provided

Feb 17, 2021

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Primary ciliary dyskinesia 7

Benign:1

Oct 18, 2024

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.18

BayesDel_addAF

Benign

-0.62

BayesDel_noAF

Benign

-0.60

CADD

Benign

(source)

DANN

Benign

0.97

DEOGEN2

Benign

0.012

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.0

FATHMM_MKL

Benign

0.052

LIST_S2

Benign

0.79

MetaRNN

Benign

0.0015

MetaSVM

Benign

-1.0

PhyloP100

2.6

PrimateAI

Benign

0.40

PROVEAN

Benign

1.7

REVEL

Benign

0.15

Sift

Benign

0.17

Vest4

0.12

MVP

0.014

ClinPred

0.0098

GERP RS

3.8

Varity_R

0.047

gMVP

0.17

Mutation Taster

=99/1

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over