7-21704421-T-G

Variant summary

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

The NM_001277115.2(DNAH11):c.6274-13T>G variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.273 in 1,594,826 control chromosomes in the GnomAD database, including 83,296 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.42 ( 19302 hom., cov: 32)

Exomes 𝑓: 0.26 ( 63994 hom. )

Consequence

DNAH11
NM_001277115.2 splice_polypyrimidine_tract, intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: 1.03

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:

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 (BayesDel_noAF=-0.83).

BP6

Variant 7-21704421-T-G is Benign according to our data. Variant chr7-21704421-T-G is described in ClinVar as [Benign]. Clinvar id is 163107.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-21704421-T-G is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.806 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DNAH11	NM_001277115.2 linkuse as main transcript	c.6274-13T>G		splice_polypyrimidine_tract_variant, intron_variant		ENST00000409508.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DNAH11	ENST00000409508.8 linkuse as main transcript	c.6274-13T>G		splice_polypyrimidine_tract_variant, intron_variant		5	NM_001277115.2	P1

Frequencies

GnomAD3 genomes

AF:

0.424

AC:

64308

AN:

151594

Hom.:

19247

Cov.:

show subpopulations

Gnomad AFR

AF:

0.813

Gnomad AMI

AF:

0.150

Gnomad AMR

AF:

0.441

Gnomad ASJ

AF:

0.175

Gnomad EAS

AF:

0.739

Gnomad SAS

AF:

0.450

Gnomad FIN

AF:

0.275

Gnomad MID

AF:

0.288

Gnomad NFE

AF:

0.200

Gnomad OTH

AF:

0.359

GnomAD3 exomes

AF:

0.390

AC:

82505

AN:

211530

Hom.:

20124

AF XY:

0.373

AC XY:

42475

AN XY:

113878

show subpopulations

Gnomad AFR exome

AF:

0.835

Gnomad AMR exome

AF:

0.564

Gnomad ASJ exome

AF:

0.193

Gnomad EAS exome

AF:

0.758

Gnomad SAS exome

AF:

0.459

Gnomad FIN exome

AF:

0.296

Gnomad NFE exome

AF:

0.223

Gnomad OTH exome

AF:

0.317

GnomAD4 exome

AF:

0.257

AC:

370622

AN:

1443116

Hom.:

63994

Cov.:

AF XY:

0.258

AC XY:

185001

AN XY:

716308

show subpopulations

Gnomad4 AFR exome

AF:

0.839

Gnomad4 AMR exome

AF:

0.524

Gnomad4 ASJ exome

AF:

0.174

Gnomad4 EAS exome

AF:

0.767

Gnomad4 SAS exome

AF:

0.428

Gnomad4 FIN exome

AF:

0.274

Gnomad4 NFE exome

AF:

0.197

Gnomad4 OTH exome

AF:

0.299

GnomAD4 genome

AF:

0.425

AC:

64433

AN:

151710

Hom.:

19302

Cov.:

AF XY:

0.431

AC XY:

31990

AN XY:

74144

show subpopulations

Gnomad4 AFR

AF:

0.813

Gnomad4 AMR

AF:

0.442

Gnomad4 ASJ

AF:

0.175

Gnomad4 EAS

AF:

0.738

Gnomad4 SAS

AF:

0.451

Gnomad4 FIN

AF:

0.275

Gnomad4 NFE

AF:

0.200

Gnomad4 OTH

AF:

0.362

Alfa

AF:

0.290

Hom.:

1788

Bravo

AF:

0.453

Asia WGS

AF:

0.601

AC:

2088

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	Mar 14, 2016	- -
Benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	Feb 21, 2013	6274-13T>G in intron 37 of DNAH11: This variant is not expected to have clinical significance because it has been identified in 22.0% (807/3666) of African Amer ican chromosomes from a broad population by the NHLBI Exome Sequencing Project ( http://evs.gs.washington.edu/EVS; dbSNP rs2965401). -

Primary ciliary dyskinesia

Benign:2

Benign, criteria provided, single submitter	clinical testing	Invitae	Feb 01, 2024	- -
Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jun 14, 2016	- -

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

Dec 31, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

Cadd

Benign

4.3

Dann

Benign

0.58

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