rs4385377

Variant names:

• chr7-21655662-G-C
• rs4385377
• NM_001277115.2:c.4945-170G>C

Your query was ambiguous. Multiple possible variants found:

• chr7-21655662-G-C
• chr7-21655662-G-T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001277115.2(DNAH11):​c.4945-170G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0528 in 152,204 control chromosomes in the GnomAD database, including 596 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: 𝑓 0.053 (596 hom., cov: 32)
• Consequence: DNAH11 NM_001277115.2 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.405
• Publications: 2 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: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 7-21655662-G-C is Benign according to our data. Variant chr7-21655662-G-C is described in ClinVar as Likely_benign. ClinVar VariationId is 1217762.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.21 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNAH11	NM_001277115.2	c.4945-170G>C		intron_variant	Intron 28 of 81	ENST00000409508.8	NP_001264044.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DNAH11	ENST00000409508.8	c.4945-170G>C		intron_variant	Intron 28 of 81	5	NM_001277115.2	ENSP00000475939.1

Frequencies

GnomAD3 genomes AF: 0.0527 AC: 8016 AN: 152086 Hom.: 590 Cov.: 32

Gnomad AFR AF: 0.0380

Gnomad AMI AF: 0.00439

Gnomad AMR AF: 0.215

Gnomad ASJ AF: 0.0320

Gnomad EAS AF: 0.168

Gnomad SAS AF: 0.0581

Gnomad FIN AF: 0.0525

Gnomad MID AF: 0.0348

Gnomad NFE AF: 0.0180

Gnomad OTH AF: 0.0499

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0528 AC: 8033 AN: 152204 Hom.: 596 Cov.: 32 AF XY: 0.0586 AC XY: 4358 AN XY: 74410

African (AFR) AF: 0.0379 AC: 1575 AN: 41542

American (AMR) AF: 0.216 AC: 3301 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.0320 AC: 111 AN: 3468

East Asian (EAS) AF: 0.168 AC: 868 AN: 5168

South Asian (SAS) AF: 0.0571 AC: 275 AN: 4818

European-Finnish (FIN) AF: 0.0525 AC: 557 AN: 10602

Middle Eastern (MID) AF: 0.0374 AC: 11 AN: 294

European-Non Finnish (NFE) AF: 0.0180 AC: 1222 AN: 68022

Other (OTH) AF: 0.0517 AC: 109 AN: 2108

Alfa AF: 0.00835 Hom.: 6

Bravo AF: 0.0664

Asia WGS AF: 0.128 AC: 445 AN: 3476

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Nov 10, 2018

GeneDx

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	9.7
DANN	Benign	0.64
PhyloP100		0.41
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs4385377; hg19: chr7-21695280;