rs190062687

Variant summary

Our verdict is Uncertain significance. Variant got 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. 17/21 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.

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

1
17
Splicing: ADA: 0.00006519
2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.953
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]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 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/exons MANE Protein UniProt
DNAH11NM_001277115.2 linkc.3765C>A p.Asp1255Glu missense_variant, splice_region_variant 19/82 ENST00000409508.8 NP_001264044.1 Q96DT5Q96NT7H9NAJ8H9NAJ7

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
DNAH11ENST00000409508.8 linkc.3765C>A p.Asp1255Glu missense_variant, splice_region_variant 19/825 NM_001277115.2 ENSP00000475939.1 Q96DT5

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Data not reliable, filtered out with message: AC0
AF:
0.00
AC:
0
AN:
1452628
Hom.:
0
Cov.:
32
AF XY:
0.00
AC XY:
0
AN XY:
721622
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32

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
T
BayesDel_noAF
Benign
-0.51
CADD
Benign
13
DANN
Benign
0.89
DEOGEN2
Benign
0.099
.;.;T
Eigen
Benign
-0.16
Eigen_PC
Benign
-0.14
FATHMM_MKL
Uncertain
0.83
D
LIST_S2
Benign
0.50
T;T;T
M_CAP
Benign
0.0097
T
MetaRNN
Benign
0.17
T;T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
1.8
.;.;L
PrimateAI
Benign
0.46
T
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
T
GERP RS
4.4
Varity_R
0.19
gMVP
0.16

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs190062687; hg19: chr7-21646160; API