rs72657303

Positions:

chr7-21600720-G-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_001277115.2(DNAH11):c.3045G>T(p.Glu1015Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00425 in 1,613,798 control chromosomes in the GnomAD database, including 22 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 (★★).

Frequency

Genomes: 𝑓 0.0030 ( 1 hom., cov: 32)

Exomes 𝑓: 0.0044 ( 21 hom. )

Consequence

DNAH11
NM_001277115.2 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: 1.60

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 (MetaRNN=0.00851959).

BP6

Variant 7-21600720-G-T is Benign according to our data. Variant chr7-21600720-G-T is described in ClinVar as [Likely_benign]. Clinvar id is 238905.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00297 (452/152264) while in subpopulation NFE AF= 0.00526 (358/68024). AF 95% confidence interval is 0.00481. There are 1 homozygotes in gnomad4. There are 195 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAdExome4 at 21 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DNAH11	NM_001277115.2 linkuse as main transcript	c.3045G>T	p.Glu1015Asp	missense_variant	16/82	ENST00000409508.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DNAH11	ENST00000409508.8 linkuse as main transcript	c.3045G>T	p.Glu1015Asp	missense_variant	16/82	5	NM_001277115.2	P1

Frequencies

GnomAD3 genomes

AF:

0.00297

AC:

452

AN:

152146

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000772

Gnomad AMI

AF:

0.00219

Gnomad AMR

AF:

0.00144

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00339

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00526

Gnomad OTH

AF:

0.000958

GnomAD3 exomes

AF:

0.00300

AC:

745

AN:

248626

Hom.:

AF XY:

0.00277

AC XY:

374

AN XY:

134846

show subpopulations

Gnomad AFR exome

AF:

0.000969

Gnomad AMR exome

AF:

0.000522

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00302

Gnomad NFE exome

AF:

0.00560

Gnomad OTH exome

AF:

0.00282

GnomAD4 exome

AF:

0.00438

AC:

6405

AN:

1461534

Hom.:

Cov.:

AF XY:

0.00418

AC XY:

3036

AN XY:

727056

show subpopulations

Gnomad4 AFR exome

AF:

0.000657

Gnomad4 AMR exome

AF:

0.000537

Gnomad4 ASJ exome

AF:

0.000153

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000464

Gnomad4 FIN exome

AF:

0.00335

Gnomad4 NFE exome

AF:

0.00540

Gnomad4 OTH exome

AF:

0.00283

GnomAD4 genome

AF:

0.00297

AC:

452

AN:

152264

Hom.:

Cov.:

AF XY:

0.00262

AC XY:

195

AN XY:

74456

show subpopulations

Gnomad4 AFR

AF:

0.000770

Gnomad4 AMR

AF:

0.00144

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00339

Gnomad4 NFE

AF:

0.00526

Gnomad4 OTH

AF:

0.000948

Alfa

AF:

0.00426

Hom.:

Bravo

AF:

0.00286

TwinsUK

AF:

0.00674

AC:

ALSPAC

AF:

0.00467

AC:

ESP6500AA

AF:

0.00102

AC:

ESP6500EA

AF:

0.00540

AC:

ExAC

AF:

0.00332

AC:

402

EpiCase

AF:

0.00442

EpiControl

AF:

0.00480

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Feb 15, 2021	This variant is associated with the following publications: (PMID: 32859249) -
Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Jun 01, 2024	DNAH11: BP4, BS2 -

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Primary ciliary dyskinesia 7

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Fulgent Genetics, Fulgent Genetics

Apr 21, 2022

- -

Primary ciliary dyskinesia

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 31, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.55

BayesDel_noAF

Benign

-0.55

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.051

.;.;T

Eigen

Benign

0.13

Eigen_PC

Benign

0.18

FATHMM_MKL

Uncertain

0.94

LIST_S2

Benign

0.41

T;T;T

M_CAP

Benign

0.011

MetaRNN

Benign

0.0085

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

2.0

.;.;M

MutationTaster

Benign

0.82

PrimateAI

Benign

0.32

PROVEAN

Benign

-1.6

.;N;.

REVEL

Benign

0.027

Sift

Benign

0.30

.;T;.

Polyphen

0.92

.;.;P

Vest4

0.36

MutPred

0.51

Gain of MoRF binding (P = 0.1357);Gain of MoRF binding (P = 0.1357);Gain of MoRF binding (P = 0.1357);

MVP

0.33

ClinPred

0.015

GERP RS

4.8

Varity_R

0.11

gMVP

0.41

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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