rs60554135

Variant names:

• chr7-21765609-G-A
• rs60554135
• NM_001277115.2:c.9102+20G>A

Your query was ambiguous. Multiple possible variants found:

• chr7-21765609-G-A
• chr7-21765609-G-T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001277115.2(DNAH11):​c.9102+20G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.107 in 1,046,238 control chromosomes in the GnomAD database, including 5,609 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.11 (475 hom., cov: 24)
  • Exomes 𝑓: 0.11 (5134 hom.)
• Consequence: DNAH11 NM_001277115.2 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -0.0290

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

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BP6: Variant 7-21765609-G-A is Benign according to our data. Variant chr7-21765609-G-A is described in ClinVar as [Benign]. Clinvar id is 257939.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-21765609-G-A is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.28 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNAH11	NM_001277115.2	c.9102+20G>A		intron_variant	Intron 55 of 81	ENST00000409508.8	NP_001264044.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DNAH11	ENST00000409508.8	c.9102+20G>A		intron_variant	Intron 55 of 81	5	NM_001277115.2	ENSP00000475939.1

Frequencies

GnomAD3 genomes AF: 0.109 AC: 9475 AN: 86780 Hom.: 474 Cov.: 24

Gnomad AFR AF: 0.0488

Gnomad AMI AF: 0.122

Gnomad AMR AF: 0.115

Gnomad ASJ AF: 0.0779

Gnomad EAS AF: 0.293

Gnomad SAS AF: 0.157

Gnomad FIN AF: 0.0889

Gnomad MID AF: 0.202

Gnomad NFE AF: 0.125

Gnomad OTH AF: 0.154

GnomAD2 exomes AF: 0.102 AC: 12758 AN: 125624 AF XY: 0.105

Gnomad AFR exome AF: 0.0313

Gnomad AMR exome AF: 0.0528

Gnomad ASJ exome AF: 0.0596

Gnomad EAS exome AF: 0.278

Gnomad FIN exome AF: 0.0688

Gnomad NFE exome AF: 0.0926

Gnomad OTH exome AF: 0.104

GnomAD4 exome AF: 0.107 AC: 102535 AN: 959374 Hom.: 5134 Cov.: 30 AF XY: 0.107 AC XY: 50816 AN XY: 475784

Gnomad4 AFR exome AF: 0.0311 AC: 832 AN: 26728

Gnomad4 AMR exome AF: 0.0569 AC: 1613 AN: 28366

Gnomad4 ASJ exome AF: 0.0725 AC: 1082 AN: 14920

Gnomad4 EAS exome AF: 0.288 AC: 9587 AN: 33314

Gnomad4 SAS exome AF: 0.104 AC: 6858 AN: 65660

Gnomad4 FIN exome AF: 0.0588 AC: 1669 AN: 28400

Gnomad4 NFE exome AF: 0.105 AC: 75472 AN: 717822

Gnomad4 Remaining exome AF: 0.118 AC: 4829 AN: 40902

GnomAD4 genome AF: 0.109 AC: 9479 AN: 86864 Hom.: 475 Cov.: 24 AF XY: 0.112 AC XY: 4607 AN XY: 41210

Gnomad4 AFR AF: 0.0488 AC: 0.0487976 AN: 0.0487976

Gnomad4 AMR AF: 0.115 AC: 0.115034 AN: 0.115034

Gnomad4 ASJ AF: 0.0779 AC: 0.0778816 AN: 0.0778816

Gnomad4 EAS AF: 0.293 AC: 0.293226 AN: 0.293226

Gnomad4 SAS AF: 0.157 AC: 0.156968 AN: 0.156968

Gnomad4 FIN AF: 0.0889 AC: 0.0888735 AN: 0.0888735

Gnomad4 NFE AF: 0.125 AC: 0.125448 AN: 0.125448

Gnomad4 OTH AF: 0.154 AC: 0.154321 AN: 0.154321

Alfa AF: 0.0359 Hom.: 36

Bravo AF: 0.0648

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Mar 15, 2016

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Primary ciliary dyskinesia 7 Benign:1

Jul 30, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Primary ciliary dyskinesia Benign:1

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided Benign:1

Aug 24, 2019

GeneDx

Significance: 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	-0.78
CADD	Benign	2.0
DANN	Benign	0.72
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

Publications

LitVar

Other links and lift over

dbSNP: rs60554135; hg19: chr7-21805227; COSMIC: COSV60957487;