rs886038473

Positions:

• chr7-21735790-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP6_Moderate

The NM_001277115.2(DNAH11):​c.7591T>C​(p.Tyr2531His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: DNAH11 NM_001277115.2 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 3.46

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP6: Variant 7-21735790-T-C is Benign according to our data. Variant chr7-21735790-T-C is described in ClinVar as [Benign]. Clinvar id is 257929.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DNAH11	NM_001277115.2	c.7591T>C	p.Tyr2531His	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.7591T>C	p.Tyr2531His	missense_variant	46/82	5	NM_001277115.2	ENSP00000475939	P1
DNAH11	ENST00000605912.1	c.151T>C	p.Tyr51His	missense_variant	1/4	3		ENSP00000476068

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 33

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.43
CADD	Benign	21
DANN	Uncertain	0.98
DEOGEN2	Benign	0.27	.;.;T;.
Eigen	Uncertain	0.19
Eigen_PC	Benign	0.079
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Benign	0.84	T;T;T;T
M_CAP	Benign	0.023	T
MetaRNN	Uncertain	0.45	T;T;T;T
MetaSVM	Benign	-0.90	T
MutationTaster	Benign	1.0	N
PrimateAI	Uncertain	0.50	T
PROVEAN	Uncertain	-3.6	.;D;.;.
REVEL	Benign	0.23
Sift	Benign	0.036	.;D;.;.
Sift4G	Pathogenic	0.0010	.;.;.;D
Vest4		0.43
MutPred		0.66		Gain of disorder (P = 0.0322);Gain of disorder (P = 0.0322);.;.;
MVP		0.41
ClinPred		0.75	D
GERP RS		5.0
Varity_R		0.12
gMVP		0.56

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: rs886038473; hg19: chr7-21775408;