7-21765609-G-T

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Strong BP6_Moderate

The NM_001277115.2(DNAH11):​c.9102+20G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000802 in 1,046,798 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00012 (0 hom., cov: 24)
  • Exomes 𝑓: 0.000077 (0 hom.)
• Consequence: DNAH11 NM_001277115.2 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• 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: Likely_benign. The variant received -6 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BP6: Variant 7-21765609-G-T is Benign according to our data. Variant chr7-21765609-G-T is described in ClinVar as Likely_benign. ClinVar VariationId is 2172776.Status of the report is criteria_provided_single_submitter, 1 stars.

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>T		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>T		intron	N/A	ENSP00000475939.1

Frequencies

GnomAD3 genomes AF: 0.000115 AC: 10 AN: 86814 Hom.: 0 Cov.: 24

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00131

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000557 AC: 70 AN: 125624 AF XY: 0.000485

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00328

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.000848

GnomAD4 exome AF: 0.0000771 AC: 74 AN: 959984 Hom.: 0 Cov.: 30 AF XY: 0.0000756 AC XY: 36 AN XY: 476030

African (AFR) AF: 0.00 AC: 0 AN: 26734

American (AMR) AF: 0.00257 AC: 73 AN: 28378

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 14918

East Asian (EAS) AF: 0.00 AC: 0 AN: 33362

South Asian (SAS) AF: 0.00 AC: 0 AN: 65678

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 28408

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3268

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 718310

Other (OTH) AF: 0.0000244 AC: 1 AN: 40928

GnomAD4 genome AF: 0.000115 AC: 10 AN: 86814 Hom.: 0 Cov.: 24 AF XY: 0.000122 AC XY: 5 AN XY: 41142

African (AFR) AF: 0.00 AC: 0 AN: 25634

American (AMR) AF: 0.00131 AC: 10 AN: 7660

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 1926

East Asian (EAS) AF: 0.00 AC: 0 AN: 4496

South Asian (SAS) AF: 0.00 AC: 0 AN: 2616

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 4334

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 198

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 38512

Other (OTH) AF: 0.00 AC: 0 AN: 1118

Alfa AF: 0.0000385 Hom.: 36

ClinVar

ClinVar submissions as Germline

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	Primary ciliary dyskinesia (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	0.76
DANN	Benign	0.69
PhyloP100		-0.029
Mutation Taster		=100/0	polymorphism

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;