rs73279826

Variant names:

• chr7-21854462-C-A
• rs73279826
• NM_001277115.2:c.11202+7C>A

Your query was ambiguous. Multiple possible variants found:

• chr7-21854462-C-A
• chr7-21854462-C-G

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.11202+7C>A variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0248 in 1,611,074 control chromosomes in the GnomAD database, including 4,470 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.093 (1893 hom., cov: 32)
  • Exomes 𝑓: 0.018 (2577 hom.)
• Consequence: DNAH11 NM_001277115.2 splice_region, intron
• Scores: Splicing: ADA: 0.00009980
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: 0.127
• Publications: 4 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: Labcorp Genetics (formerly Invitae), ClinGen, Laboratory for Molecular Medicine
• 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=-0.76).
• BP6: Variant 7-21854462-C-A is Benign according to our data. Variant chr7-21854462-C-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 163123.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAH11	NM_001277115.2	MANE Select	c.11202+7C>A		splice_region intron	N/A	NP_001264044.1	Q96DT5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAH11	ENST00000409508.8	TSL:5 MANE Select	c.11202+7C>A		splice_region intron	N/A	ENSP00000475939.1	Q96DT5
	DNAH11	ENST00000421290.1	TSL:4	n.385+7C>A		splice_region intron	N/A
	DNAH11	ENST00000607413.5	TSL:4	n.465+7C>A		splice_region intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0934 AC: 14182 AN: 151912 Hom.: 1894 Cov.: 32

Gnomad AFR AF: 0.285

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0348

Gnomad ASJ AF: 0.00691

Gnomad EAS AF: 0.220

Gnomad SAS AF: 0.0118

Gnomad FIN AF: 0.0303

Gnomad MID AF: 0.0510

Gnomad NFE AF: 0.00256

Gnomad OTH AF: 0.0702

GnomAD2 exomes AF: 0.0427 AC: 10571 AN: 247478 AF XY: 0.0359

Gnomad AFR exome AF: 0.291

Gnomad AMR exome AF: 0.0238

Gnomad ASJ exome AF: 0.00847

Gnomad EAS exome AF: 0.221

Gnomad FIN exome AF: 0.0303

Gnomad NFE exome AF: 0.00253

Gnomad OTH exome AF: 0.0246

GnomAD4 exome AF: 0.0177 AC: 25775 AN: 1459044 Hom.: 2577 Cov.: 34 AF XY: 0.0162 AC XY: 11742 AN XY: 725618

African (AFR) AF: 0.293 AC: 9739 AN: 33272

American (AMR) AF: 0.0247 AC: 1098 AN: 44502

Ashkenazi Jewish (ASJ) AF: 0.00824 AC: 215 AN: 26098

East Asian (EAS) AF: 0.218 AC: 8599 AN: 39522

South Asian (SAS) AF: 0.00567 AC: 484 AN: 85422

European-Finnish (FIN) AF: 0.0279 AC: 1486 AN: 53298

Middle Eastern (MID) AF: 0.0184 AC: 106 AN: 5762

European-Non Finnish (NFE) AF: 0.00161 AC: 1794 AN: 1110912

Other (OTH) AF: 0.0374 AC: 2254 AN: 60256

GnomAD4 genome AF: 0.0933 AC: 14183 AN: 152030 Hom.: 1893 Cov.: 32 AF XY: 0.0933 AC XY: 6939 AN XY: 74334

African (AFR) AF: 0.285 AC: 11776 AN: 41388

American (AMR) AF: 0.0348 AC: 532 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.00691 AC: 24 AN: 3472

East Asian (EAS) AF: 0.220 AC: 1139 AN: 5166

South Asian (SAS) AF: 0.0114 AC: 55 AN: 4812

European-Finnish (FIN) AF: 0.0303 AC: 321 AN: 10588

Middle Eastern (MID) AF: 0.0548 AC: 16 AN: 292

European-Non Finnish (NFE) AF: 0.00254 AC: 173 AN: 67994

Other (OTH) AF: 0.0695 AC: 147 AN: 2116

Alfa AF: 0.0345 Hom.: 291

Bravo AF: 0.105

Asia WGS AF: 0.107 AC: 372 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	2	not specified (2)
-	-	2	Primary ciliary dyskinesia (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	0.99
DANN	Benign	0.59
PhyloP100		0.13
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00010
dbscSNV1_RF	Benign	0.0
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: rs73279826; hg19: chr7-21894080; COSMIC: COSV60946520;