NM_001277115.2:c.12387+20T>A

Variant names:

• chr7-21880913-T-A
• rs116529653
• NM_001277115.2:c.12387+20T>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_001277115.2(DNAH11):​c.12387+20T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00242 in 1,577,946 control chromosomes in the GnomAD database, including 85 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.013 (39 hom., cov: 33)
  • Exomes 𝑓: 0.0013 (46 hom.)
• Consequence: DNAH11 NM_001277115.2 intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.0400
• Publications: 0 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=-0.83).
• BP6: Variant 7-21880913-T-A is Benign according to our data. Variant chr7-21880913-T-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 257860.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.013 (1976/152350) while in subpopulation AFR AF = 0.0446 (1854/41588). AF 95% confidence interval is 0.0429. There are 39 homozygotes in GnomAd4. There are 953 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 39 AR,AD gene

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAH11	NM_001277115.2	MANE Select	c.12387+20T>A		intron	N/A	NP_001264044.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAH11	ENST00000409508.8	TSL:5 MANE Select	c.12387+20T>A		intron	N/A	ENSP00000475939.1

Frequencies

GnomAD3 genomes AF: 0.0130 AC: 1979 AN: 152232 Hom.: 39 Cov.: 33

Gnomad AFR AF: 0.0448

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00530

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.000206

Gnomad OTH AF: 0.0115

GnomAD2 exomes AF: 0.00362 AC: 753 AN: 207932 AF XY: 0.00263

Gnomad AFR exome AF: 0.0474

Gnomad AMR exome AF: 0.00306

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000183

Gnomad OTH exome AF: 0.00158

GnomAD4 exome AF: 0.00129 AC: 1838 AN: 1425596 Hom.: 46 Cov.: 29 AF XY: 0.00113 AC XY: 798 AN XY: 707722

African (AFR) AF: 0.0451 AC: 1413 AN: 31330

American (AMR) AF: 0.00298 AC: 101 AN: 33930

Ashkenazi Jewish (ASJ) AF: 0.0000403 AC: 1 AN: 24802

East Asian (EAS) AF: 0.00 AC: 0 AN: 39260

South Asian (SAS) AF: 0.0000632 AC: 5 AN: 79118

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53054

Middle Eastern (MID) AF: 0.00224 AC: 12 AN: 5360

European-Non Finnish (NFE) AF: 0.000130 AC: 143 AN: 1099718

Other (OTH) AF: 0.00276 AC: 163 AN: 59024

GnomAD4 genome AF: 0.0130 AC: 1976 AN: 152350 Hom.: 39 Cov.: 33 AF XY: 0.0128 AC XY: 953 AN XY: 74506

African (AFR) AF: 0.0446 AC: 1854 AN: 41588

American (AMR) AF: 0.00529 AC: 81 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10628

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.000206 AC: 14 AN: 68028

Other (OTH) AF: 0.0113 AC: 24 AN: 2116

Alfa AF: 0.00619 Hom.: 2

Bravo AF: 0.0150

Asia WGS AF: 0.00173 AC: 6 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign/Likely 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)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	2.5
DANN	Benign	0.56
PhyloP100		0.040
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: rs116529653; hg19: chr7-21920531;