rs72658840

Positions:

chr7-21901250-C-T

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

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]

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 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
DNAH11	NM_001277115.2 linkuse as main transcript	c.13547C>T	p.Ala4516Val	missense_variant	82/82	ENST00000409508.8	NP_001264044.1
CDCA7L	NM_018719.5 linkuse as main transcript	c.*1072G>A		3_prime_UTR_variant	10/10	ENST00000406877.8	NP_061189.2
CDCA7L	NM_001127370.3 linkuse as main transcript	c.*1072G>A		3_prime_UTR_variant	11/11		NP_001120842.1
CDCA7L	NM_001127371.3 linkuse as main transcript	c.*1072G>A		3_prime_UTR_variant	9/9		NP_001120843.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DNAH11	ENST00000409508.8 linkuse as main transcript	c.13547C>T	p.Ala4516Val	missense_variant	82/82	5	NM_001277115.2	ENSP00000475939	P1
CDCA7L	ENST00000406877.8 linkuse as main transcript	c.*1072G>A		3_prime_UTR_variant	10/10	1	NM_018719.5	ENSP00000383986	P1	Q96GN5-1
CDCA7L	ENST00000356195.9 linkuse as main transcript	c.*1072G>A		3_prime_UTR_variant	11/11	2		ENSP00000348523		Q96GN5-4
CDCA7L	ENST00000488845.1 linkuse as main transcript	n.1594G>A		non_coding_transcript_exon_variant	4/4	2

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

GnomAD3 exomes

AF:

0.00685

AC:

1641

AN:

239448

Hom.:

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.:

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.:

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.:

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

Benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	Feb 21, 2013	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). -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -

Primary ciliary dyskinesia

Benign:2

Likely benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jun 14, 2016	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Feb 17, 2021	- -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Primary ciliary dyskinesia 7

Benign:1

Benign, criteria provided, single submitter

clinical testing

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Nov 03, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.18

BayesDel_addAF

Benign

-0.62

BayesDel_noAF

Benign

-0.60

CADD

Benign

DANN

Benign

0.97

DEOGEN2

Benign

0.012

.;.;T

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.0

FATHMM_MKL

Benign

0.052

LIST_S2

Benign

0.79

T;T;T

MetaRNN

Benign

0.0015

T;T;T

MetaSVM

Benign

-1.0

MutationTaster

Benign

0.96

N;N;N

PrimateAI

Benign

0.40

PROVEAN

Benign

1.7

.;N;.

REVEL

Benign

0.15

Sift

Benign

0.17

.;T;.

Vest4

0.12

MVP

0.014

ClinPred

0.0098

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over