Variant rs143830019 details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_001277115.2(DNAH11):c.3634T>C(p.Tyr1212His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000667 in 1,579,026 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.00065 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00067 ( 3 hom. )

Consequence

DNAH11
NM_001277115.2 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 2.08

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=0.003771484).

BP6

Variant 7-21601604-T-C is Benign according to our data. Variant chr7-21601604-T-C is described in ClinVar as [Benign]. Clinvar id is 257883.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.00065 (99/152328) while in subpopulation EAS AF= 0.0116 (60/5184). AF 95% confidence interval is 0.00923. There are 0 homozygotes in gnomad4. There are 55 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAdExome4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DNAH11	NM_001277115.2 linkuse as main transcript	c.3634T>C	p.Tyr1212His	missense_variant	18/82	ENST00000409508.8	NP_001264044.1	Q96DT5Q96NT7H9NAJ8H9NAJ7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DNAH11	ENST00000409508.8 linkuse as main transcript	c.3634T>C	p.Tyr1212His	missense_variant	18/82	5	NM_001277115.2	ENSP00000475939.1		Q96DT5

Frequencies

GnomAD3 genomes

AF:

0.000650

AC:

AN:

152210

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.0115

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00292

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000118

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00126

AC:

286

AN:

227500

Hom.:

AF XY:

0.00117

AC XY:

144

AN XY:

122860

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0105

Gnomad SAS exome

AF:

0.000154

Gnomad FIN exome

AF:

0.00375

Gnomad NFE exome

AF:

0.000229

Gnomad OTH exome

AF:

0.000368

GnomAD4 exome

AF:

0.000669

AC:

954

AN:

1426698

Hom.:

Cov.:

AF XY:

0.000641

AC XY:

451

AN XY:

703978

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0170

Gnomad4 SAS exome

AF:

0.000134

Gnomad4 FIN exome

AF:

0.00349

Gnomad4 NFE exome

AF:

0.0000614

Gnomad4 OTH exome

AF:

0.000476

GnomAD4 genome

AF:

0.000650

AC:

AN:

152328

Hom.:

Cov.:

AF XY:

0.000738

AC XY:

AN XY:

74494

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.0116

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00292

Gnomad4 NFE

AF:

0.000118

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000540

Hom.:

Bravo

AF:

0.000536

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000259

AC:

ExAC

AF:

0.00103

AC:

124

Asia WGS

AF:

0.00549

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

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

0.099

BayesDel_addAF

Benign

-0.53

BayesDel_noAF

Benign

-0.52

CADD

Benign

DANN

Benign

0.93

DEOGEN2

Benign

0.022

.;.;T

Eigen

Uncertain

0.33

Eigen_PC

Uncertain

0.33

FATHMM_MKL

Uncertain

0.94

LIST_S2

Benign

0.75

T;T;T

MetaRNN

Benign

0.0038

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.4

.;.;L

PrimateAI

Uncertain

0.56

PROVEAN

Benign

-0.27

.;N;.

REVEL

Benign

0.086

Sift

Benign

0.63

.;T;.

Polyphen

1.0

.;.;D

Vest4

0.33

MVP

0.32

ClinPred

0.053

GERP RS

4.5

Varity_R

0.090

gMVP

0.40

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