dbSNP rs190062687: DNAH11:p.Asp1255Glu (chr7-21606542-C-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001277115.2(DNAH11):c.3765C>A(p.Asp1255Glu) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 18/23 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. D1255D) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

DNAH11
NM_001277115.2 missense, splice_region

Scores

Splicing: ADA: 0.00006519

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.953

Publications

2 publications found

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 Gene-Disease associations (from GenCC):

primary ciliary dyskinesia 7
Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: PanelApp Australia, Laboratory for Molecular Medicine, Labcorp Genetics (formerly Invitae), ClinGen
primary ciliary dyskinesia
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

DNAH11 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.17114246).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNAH11	NM_001277115.2 link	c.3765C>A	p.Asp1255Glu	missense_variant, splice_region_variant	Exon 19 of 82	ENST00000409508.8	NP_001264044.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DNAH11	ENST00000409508.8 link	c.3765C>A	p.Asp1255Glu	missense_variant, splice_region_variant	Exon 19 of 82	5	NM_001277115.2	ENSP00000475939.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1452628

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

721622

African (AFR)

AF:

0.00

AC:

AN:

33190

American (AMR)

AF:

0.00

AC:

AN:

43580

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25982

East Asian (EAS)

AF:

0.00

AC:

AN:

39610

South Asian (SAS)

AF:

0.00

AC:

AN:

83226

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52232

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5754

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1108930

Other (OTH)

AF:

0.00

AC:

AN:

60124

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.16

BayesDel_addAF

Benign

-0.19

BayesDel_noAF

Benign

-0.51

CADD

Benign

(source)

DANN

Benign

0.89

DEOGEN2

Benign

0.099

.;.;T

Eigen

Benign

-0.16

Eigen_PC

Benign

-0.14

FATHMM_MKL

Uncertain

0.83

LIST_S2

Benign

0.50

T;T;T

M_CAP

Benign

0.0097

MetaRNN

Benign

0.17

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.8

.;.;L

PhyloP100

0.95

PrimateAI

Benign

0.46

PROVEAN

Benign

-1.6

.;N;.

REVEL

Benign

0.14

Sift

Benign

0.49

.;T;.

Polyphen

0.0010

.;.;B

Vest4

0.23

MutPred

0.49

Gain of methylation at K1250 (P = 0.1104);Gain of methylation at K1250 (P = 0.1104);Gain of methylation at K1250 (P = 0.1104);

MVP

0.34

ClinPred

0.38

GERP RS

4.4

Varity_R

0.19

gMVP

0.16

Mutation Taster

=63/37

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000065

dbscSNV1_RF

Benign

0.12

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over