chr7-21765609-G-A

Variant names:

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

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
• Publications: 3 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 -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 VariationId is 257939.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.28 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001277115.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAH11	NM_001277115.2	MANE Select	c.9102+20G>A		intron	N/A	NP_001264044.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAH11	ENST00000409508.8	TSL:5 MANE Select	c.9102+20G>A		intron	N/A	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

African (AFR) AF: 0.0311 AC: 832 AN: 26728

American (AMR) AF: 0.0569 AC: 1613 AN: 28366

Ashkenazi Jewish (ASJ) AF: 0.0725 AC: 1082 AN: 14920

East Asian (EAS) AF: 0.288 AC: 9587 AN: 33314

South Asian (SAS) AF: 0.104 AC: 6858 AN: 65660

European-Finnish (FIN) AF: 0.0588 AC: 1669 AN: 28400

Middle Eastern (MID) AF: 0.182 AC: 593 AN: 3262

European-Non Finnish (NFE) AF: 0.105 AC: 75472 AN: 717822

Other (OTH) 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

African (AFR) AF: 0.0488 AC: 1254 AN: 25698

American (AMR) AF: 0.115 AC: 883 AN: 7676

Ashkenazi Jewish (ASJ) AF: 0.0779 AC: 150 AN: 1926

East Asian (EAS) AF: 0.293 AC: 1316 AN: 4488

South Asian (SAS) AF: 0.157 AC: 410 AN: 2612

European-Finnish (FIN) AF: 0.0889 AC: 385 AN: 4332

Middle Eastern (MID) AF: 0.207 AC: 38 AN: 184

European-Non Finnish (NFE) AF: 0.125 AC: 4829 AN: 38494

Other (OTH) AF: 0.154 AC: 175 AN: 1134

Alfa AF: 0.0359 Hom.: 36

Bravo AF: 0.0648

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)
-	-	1	not specified (1)
-	-	1	Primary ciliary dyskinesia (1)
-	-	1	Primary ciliary dyskinesia 7 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	2.0
DANN	Benign	0.72
PhyloP100		-0.029
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: rs60554135; hg19: chr7-21805227; COSMIC: COSV60957487;