rs773705030

chr7-21571882-A-G

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_Moderate BP6_Moderate

The NM_001277115.2(DNAH11):c.1502A>G(p.Asn501Ser) variant causes a missense change. The variant allele was found at a frequency of 0.000037 in 1,460,970 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. N501K) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.000037 (2 hom.)
• Consequence: DNAH11 NM_001277115.2 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 5.27

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]

LOC105375183 (HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0707438).
• BP6: Variant 7-21571882-A-G is Benign according to our data. Variant chr7-21571882-A-G is described in ClinVar as [Benign]. Clinvar id is 525224.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DNAH11	NM_001277115.2	c.1502A>G	p.Asn501Ser	missense_variant	8/82	ENST00000409508.8
LOC105375183	XR_007060247.1	n.282+1444T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DNAH11	ENST00000409508.8	c.1502A>G	p.Asn501Ser	missense_variant	8/82	5	NM_001277115.2	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.0000604 AC: 15 AN: 248154 Hom.: 0 AF XY: 0.000104 AC XY: 14 AN XY: 134618

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000491

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000370 AC: 54 AN: 1460970 Hom.: 2 Cov.: 31 AF XY: 0.0000564 AC XY: 41 AN XY: 726764

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000580

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000270

Gnomad4 OTH exome AF: 0.0000166

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ExAC AF: 0.0000662 AC: 8

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Primary ciliary dyskinesia Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Sep 08, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.079
BayesDel_addAF	Benign	-0.45	T
BayesDel_noAF	Benign	-0.55
Cadd	Benign	15
Dann	Benign	0.20
Eigen	Benign	-0.39
Eigen_PC	Benign	-0.18
FATHMM_MKL	Benign	0.74	D
LIST_S2	Benign	0.77	T;T;T
M_CAP	Benign	0.0055	T
MetaRNN	Benign	0.071	T;T;T
MetaSVM	Benign	-1.0	T
MutationTaster	Benign	0.98	D
PrimateAI	Benign	0.42	T
Polyphen		0.059	.;.;B
Vest4		0.42
MutPred		0.56		Gain of disorder (P = 0.0412);Gain of disorder (P = 0.0412);Gain of disorder (P = 0.0412);
MVP		0.38
ClinPred		0.060	T
GERP RS		5.9
Varity_R		0.12
gMVP		0.039

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: rs773705030; hg19: chr7-21611500;