rs762297426

Variant names:

• chr7-21854360-G-A
• rs762297426
• NM_001277115.2:c.11107G>A

Your query was ambiguous. Multiple possible variants found:

• chr7-21854360-G-A
• chr7-21854360-G-C

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001277115.2(DNAH11):​c.11107G>A​(p.Glu3703Lys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. E3703Q) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 33)
• Consequence: DNAH11 NM_001277115.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 8.02
• Publications: 0 publications found

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

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNAH11	NM_001277115.2	c.11107G>A	p.Glu3703Lys	missense_variant	Exon 68 of 82	ENST00000409508.8	NP_001264044.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DNAH11	ENST00000409508.8	c.11107G>A	p.Glu3703Lys	missense_variant	Exon 68 of 82	5	NM_001277115.2	ENSP00000475939.1
DNAH11	ENST00000421290.1	n.290G>A		non_coding_transcript_exon_variant	Exon 3 of 4	4
DNAH11	ENST00000607413.5	n.370G>A		non_coding_transcript_exon_variant	Exon 3 of 4	4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Primary ciliary dyskinesia Uncertain:1

May 30, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The p.E3703K variant (also known as c.11107G>A), located in coding exon 68 of the DNAH11 gene, results from a G to A substitution at nucleotide position 11107. The glutamic acid at codon 3703 is replaced by lysine, an amino acid with similar properties. This amino acid position is conserved. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.31
BayesDel_addAF	Uncertain	0.13	D
BayesDel_noAF	Uncertain	-0.050
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.38	.;.;T
Eigen	Uncertain	0.35
Eigen_PC	Uncertain	0.43
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Pathogenic	0.99	D;D;D
M_CAP	Benign	0.060	D
MetaRNN	Uncertain	0.60	D;D;D
MetaSVM	Benign	-0.67	T
PhyloP100		8.0
PrimateAI	Uncertain	0.52	T
PROVEAN	Uncertain	-3.8	.;D;.
REVEL	Uncertain	0.59
Sift	Uncertain	0.0020	.;D;.
Vest4		0.68
MutPred		0.51		Gain of MoRF binding (P = 0.0026);Gain of MoRF binding (P = 0.0026);.;
MVP		0.83
ClinPred		0.99	D
GERP RS		4.7
Varity_R		0.43
gMVP		0.56
Mutation Taster		=79/21	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs762297426; hg19: chr7-21893978;