rs4722064

Positions:

• chr7-21854375-G-C
• chr7-21854375-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001277115.2(DNAH11):​c.11122G>C​(p.Val3708Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Benignin Lovd.

• Frequency: Genomes: not found (cov: 31)
• Consequence: DNAH11 NM_001277115.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.28

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 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DNAH11	NM_001277115.2	c.11122G>C	p.Val3708Leu	missense_variant	68/82	ENST00000409508.8	NP_001264044.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DNAH11	ENST00000409508.8	c.11122G>C	p.Val3708Leu	missense_variant	68/82	5	NM_001277115.2	ENSP00000475939	P1
DNAH11	ENST00000421290.1	n.305G>C		non_coding_transcript_exon_variant	3/4	4
DNAH11	ENST00000607413.5	n.385G>C		non_coding_transcript_exon_variant	3/4	4

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 47

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.32
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.45
CADD	Uncertain	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.18	.;.;T
Eigen	Uncertain	0.43
Eigen_PC	Uncertain	0.51
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Benign	0.61	T;T;T
M_CAP	Benign	0.0099	T
MetaRNN	Uncertain	0.43	T;T;T
MetaSVM	Benign	-0.92	T
MutationTaster	Benign	0.00023	P
PrimateAI	Benign	0.35	T
PROVEAN	Benign	-1.8	.;N;.
REVEL	Benign	0.10
Sift	Uncertain	0.010	.;D;.
Vest4		0.14
MutPred		0.42		Gain of glycosylation at P3714 (P = 0.1154);Gain of glycosylation at P3714 (P = 0.1154);.;
MVP		0.30
ClinPred		0.98	D
GERP RS		5.7
Varity_R		0.29
gMVP		0.54

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

Other links and lift over

dbSNP: rs4722064; hg19: chr7-21893993;