7-21854375-G-T

Position:

chr7-21854375-G-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.11122G>T(p.Val3708Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.64 in 1,613,110 control chromosomes in the GnomAD database, including 339,412 homozygotes. In-silico tool predicts a benign outcome for this variant. 10/17 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.57 ( 25986 hom., cov: 31)

Exomes 𝑓: 0.65 ( 313426 hom. )

Consequence

DNAH11
NM_001277115.2 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: 3.28

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:

DNAH11 (HGNC:):

DNAH11 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=8.795036E-6).

BP6

Variant 7-21854375-G-T is Benign according to our data. Variant chr7-21854375-G-T is described in ClinVar as [Benign]. Clinvar id is 163121.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-21854375-G-T is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.676 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DNAH11	NM_001277115.2 linkuse as main transcript	c.11122G>T	p.Val3708Leu	missense_variant	68/82	ENST00000409508.8	NP_001264044.1	Q96DT5Q96NT7H9NAJ8H9NAJ7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
DNAH11	ENST00000409508.8 linkuse as main transcript	c.11122G>T	p.Val3708Leu	missense_variant	68/82	5	NM_001277115.2	ENSP00000475939.1	Q96DT5
DNAH11	ENST00000421290.1 linkuse as main transcript	n.305G>T		non_coding_transcript_exon_variant	3/4	4
DNAH11	ENST00000607413.5 linkuse as main transcript	n.385G>T		non_coding_transcript_exon_variant	3/4	4

Frequencies

GnomAD3 genomes

AF:

0.570

AC:

86483

AN:

151744

Hom.:

25988

Cov.:

show subpopulations

Gnomad AFR

AF:

0.413

Gnomad AMI

AF:

0.669

Gnomad AMR

AF:

0.533

Gnomad ASJ

AF:

0.677

Gnomad EAS

AF:

0.332

Gnomad SAS

AF:

0.444

Gnomad FIN

AF:

0.638

Gnomad MID

AF:

0.639

Gnomad NFE

AF:

0.681

Gnomad OTH

AF:

0.616

GnomAD3 exomes

AF:

0.571

AC:

141939

AN:

248784

Hom.:

42710

AF XY:

0.576

AC XY:

77722

AN XY:

134980

show subpopulations

Gnomad AFR exome

AF:

0.401

Gnomad AMR exome

AF:

0.458

Gnomad ASJ exome

AF:

0.671

Gnomad EAS exome

AF:

0.325

Gnomad SAS exome

AF:

0.455

Gnomad FIN exome

AF:

0.630

Gnomad NFE exome

AF:

0.676

Gnomad OTH exome

AF:

0.616

GnomAD4 exome

AF:

0.648

AC:

946188

AN:

1461248

Hom.:

313426

Cov.:

AF XY:

0.643

AC XY:

467741

AN XY:

726928

show subpopulations

Gnomad4 AFR exome

AF:

0.406

Gnomad4 AMR exome

AF:

0.469

Gnomad4 ASJ exome

AF:

0.666

Gnomad4 EAS exome

AF:

0.343

Gnomad4 SAS exome

AF:

0.459

Gnomad4 FIN exome

AF:

0.633

Gnomad4 NFE exome

AF:

0.689

Gnomad4 OTH exome

AF:

0.621

GnomAD4 genome

AF:

0.570

AC:

86504

AN:

151862

Hom.:

25986

Cov.:

AF XY:

0.559

AC XY:

41488

AN XY:

74200

show subpopulations

Gnomad4 AFR

AF:

0.413

Gnomad4 AMR

AF:

0.532

Gnomad4 ASJ

AF:

0.677

Gnomad4 EAS

AF:

0.331

Gnomad4 SAS

AF:

0.444

Gnomad4 FIN

AF:

0.638

Gnomad4 NFE

AF:

0.681

Gnomad4 OTH

AF:

0.610

Alfa

AF:

0.650

Hom.:

55434

Bravo

AF:

0.556

TwinsUK

AF:

0.697

AC:

2586

ALSPAC

AF:

0.683

AC:

2634

ESP6500AA

AF:

0.421

AC:

1548

ESP6500EA

AF:

0.679

AC:

5556

ExAC

AF:

0.570

AC:

68826

Asia WGS

AF:

0.357

AC:

1244

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:4

Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -
Benign, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -
Benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	Feb 21, 2013	Val3708Leu in exon 68 of DNAH11: This variant is not expected to have clinical s ignificance because it has been identified in 42.1% (1548/3680) of African Ameri can chromosomes from a broad population by the NHLBI Exome Sequencing Project (h ttp://evs.gs.washington.edu/EVS; dbSNP rs4722064). -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -

Primary ciliary dyskinesia

Benign:2

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	Feb 01, 2024	- -

Primary ciliary dyskinesia 7

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 30, 2021

- -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 10, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.32

BayesDel_addAF

Benign

-0.57

BayesDel_noAF

Benign

-0.45

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.18

.;.;T

Eigen

Uncertain

0.43

Eigen_PC

Uncertain

0.51

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Benign

0.61

T;T;T

MetaRNN

Benign

0.0000088

T;T;T

MetaSVM

Benign

-0.98

PrimateAI

Benign

0.35

PROVEAN

Benign

-1.8

.;N;.

REVEL

Benign

0.068

Sift

Uncertain

0.010

.;D;.

Vest4

0.14

MutPred

0.42

Gain of glycosylation at P3714 (P = 0.1154);Gain of glycosylation at P3714 (P = 0.1154);.;

ClinPred

0.013

GERP RS

5.7

Varity_R

0.29

gMVP

0.54

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