NM_001277115.2:c.12530C>T

Variant names:

• chr7-21892447-C-T
• rs886038458
• NM_001277115.2:c.12530C>T

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 2P and 3B. PM2 BP4 BP6_Moderate

The NM_001277115.2(DNAH11):​c.12530C>T​(p.Ala4177Val) variant causes a missense 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. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: DNAH11 NM_001277115.2 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.98
• 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: Likely_benign. The variant received -1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.36515617).
• BP6: Variant 7-21892447-C-T is Benign according to our data. Variant chr7-21892447-C-T is described in ClinVar as Benign. ClinVar VariationId is 257864.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNAH11	NM_001277115.2	c.12530C>T	p.Ala4177Val	missense_variant	Exon 77 of 82	ENST00000409508.8	NP_001264044.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DNAH11	ENST00000409508.8	c.12530C>T	p.Ala4177Val	missense_variant	Exon 77 of 82	5	NM_001277115.2	ENSP00000475939.1
DNAH11	ENST00000479878.1	n.-178C>T		upstream_gene_variant		3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

-

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.24
BayesDel_addAF	Benign	-0.095	T
BayesDel_noAF	Benign	-0.37
CADD	Benign	23
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.19	.;.;T
Eigen	Uncertain	0.57
Eigen_PC	Uncertain	0.61
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Uncertain	0.95	D;D;D
M_CAP	Benign	0.039	D
MetaRNN	Benign	0.37	T;T;T
MetaSVM	Benign	-1.2	T
PhyloP100		3.0
PrimateAI	Uncertain	0.50	T
PROVEAN	Uncertain	-3.5	.;D;.
REVEL	Benign	0.25
Sift	Uncertain	0.015	.;D;.
Vest4		0.31
MutPred		0.68		Loss of catalytic residue at M4182 (P = 0.0605);Loss of catalytic residue at M4182 (P = 0.0605);.;
MVP		0.44
ClinPred		0.78	D
GERP RS		6.1
Varity_R		0.46
gMVP		0.23
Mutation Taster		=52/48	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		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: rs886038458; hg19: chr7-21932065;