NM_001277115.2:c.7335G>A

Variant names:

• chr7-21725879-G-A
• rs11768670
• NM_001277115.2:c.7335G>A

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BA1

The NM_001277115.2(DNAH11):​c.7335G>A​(p.Ser2445Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.218 in 1,607,404 control chromosomes in the GnomAD database, including 40,519 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Synonymous variant affecting the same amino acid position (i.e. S2445S) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.20 (3233 hom., cov: 32)
  • Exomes 𝑓: 0.22 (37286 hom.)
• Consequence: DNAH11 NM_001277115.2 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: -0.613
• Publications: 9 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 -19 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.32).
• BP6: Variant 7-21725879-G-A is Benign according to our data. Variant chr7-21725879-G-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 178728.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.613 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.237 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.7335G>A	p.Ser2445Ser	synonymous	Exon 45 of 82	NP_001264044.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAH11	ENST00000409508.8	TSL:5 MANE Select	c.7335G>A	p.Ser2445Ser	synonymous	Exon 45 of 82	ENSP00000475939.1

Frequencies

GnomAD3 genomes AF: 0.197 AC: 29924 AN: 151894 Hom.: 3233 Cov.: 32

Gnomad AFR AF: 0.141

Gnomad AMI AF: 0.212

Gnomad AMR AF: 0.183

Gnomad ASJ AF: 0.209

Gnomad EAS AF: 0.0566

Gnomad SAS AF: 0.0963

Gnomad FIN AF: 0.272

Gnomad MID AF: 0.187

Gnomad NFE AF: 0.240

Gnomad OTH AF: 0.195

GnomAD2 exomes AF: 0.189 AC: 45161 AN: 238888 AF XY: 0.190

Gnomad AFR exome AF: 0.137

Gnomad AMR exome AF: 0.135

Gnomad ASJ exome AF: 0.212

Gnomad EAS exome AF: 0.0521

Gnomad FIN exome AF: 0.270

Gnomad NFE exome AF: 0.240

Gnomad OTH exome AF: 0.206

GnomAD4 exome AF: 0.221 AC: 321286 AN: 1455392 Hom.: 37286 Cov.: 37 AF XY: 0.218 AC XY: 157476 AN XY: 723162

African (AFR) AF: 0.133 AC: 4435 AN: 33428

American (AMR) AF: 0.143 AC: 6276 AN: 43978

Ashkenazi Jewish (ASJ) AF: 0.213 AC: 5531 AN: 25962

East Asian (EAS) AF: 0.0704 AC: 2788 AN: 39618

South Asian (SAS) AF: 0.105 AC: 8917 AN: 84728

European-Finnish (FIN) AF: 0.269 AC: 14273 AN: 53118

Middle Eastern (MID) AF: 0.195 AC: 1122 AN: 5764

European-Non Finnish (NFE) AF: 0.240 AC: 265709 AN: 1108660

Other (OTH) AF: 0.203 AC: 12235 AN: 60136

GnomAD4 genome AF: 0.197 AC: 29926 AN: 152012 Hom.: 3233 Cov.: 32 AF XY: 0.195 AC XY: 14484 AN XY: 74284

African (AFR) AF: 0.140 AC: 5819 AN: 41474

American (AMR) AF: 0.183 AC: 2787 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.209 AC: 726 AN: 3468

East Asian (EAS) AF: 0.0567 AC: 294 AN: 5186

South Asian (SAS) AF: 0.0961 AC: 463 AN: 4816

European-Finnish (FIN) AF: 0.272 AC: 2861 AN: 10514

Middle Eastern (MID) AF: 0.187 AC: 55 AN: 294

European-Non Finnish (NFE) AF: 0.240 AC: 16321 AN: 67968

Other (OTH) AF: 0.193 AC: 407 AN: 2112

Alfa AF: 0.218 Hom.: 16941

Bravo AF: 0.189

Asia WGS AF: 0.0830 AC: 290 AN: 3478

ClinVar

ClinVar submissions as Germline

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	-0.32
CADD	Benign	8.3
DANN	Benign	0.75
PhyloP100		-0.61
Mutation Taster		=98/2	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: rs11768670; hg19: chr7-21765497; COSMIC: COSV60955953;