rs752787517

Positions:

• chr7-21735655-A-C
• chr7-21735655-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_001277115.2(DNAH11):​c.7456A>C​(p.Thr2486Pro) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: DNAH11 NM_001277115.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.35

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.748

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DNAH11	NM_001277115.2	c.7456A>C	p.Thr2486Pro	missense_variant	46/82	ENST00000409508.8	NP_001264044.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DNAH11	ENST00000409508.8	c.7456A>C	p.Thr2486Pro	missense_variant	46/82	5	NM_001277115.2	ENSP00000475939	P1
DNAH11	ENST00000605912.1	c.16A>C	p.Thr6Pro	missense_variant	1/4	3		ENSP00000476068

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.34
BayesDel_addAF	Uncertain	0.12	D
BayesDel_noAF	Uncertain	-0.070
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.60	.;.;D;.
Eigen	Uncertain	0.66
Eigen_PC	Uncertain	0.65
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Pathogenic	0.97	D;D;D;D
M_CAP	Benign	0.050	D
MetaRNN	Pathogenic	0.75	D;D;D;D
MetaSVM	Benign	-0.54	T
MutationTaster	Benign	0.99	D
PrimateAI	Benign	0.41	T
PROVEAN	Pathogenic	-5.6	.;D;.;.
REVEL	Uncertain	0.36
Sift	Uncertain	0.0010	.;D;.;.
Sift4G	Uncertain	0.0050	.;.;.;D
Vest4		0.76
MutPred		0.54		Loss of catalytic residue at T2493 (P = 0.0022);Loss of catalytic residue at T2493 (P = 0.0022);.;.;
MVP		0.48
ClinPred		1.0	D
GERP RS		5.0
Varity_R		0.91
gMVP		0.74

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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

Other links and lift over

dbSNP: rs752787517; hg19: chr7-21775273;