NM_001277115.2:c.13128C>A

Variant names:

• chr7-21899414-C-A
• rs56333627
• NM_001277115.2:c.13128C>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.13128C>A​(p.Leu4376Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.297 in 1,613,276 control chromosomes in the GnomAD database, including 74,262 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. L4376L) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.25 (5447 hom., cov: 32)
  • Exomes 𝑓: 0.30 (68815 hom.)
• Consequence: DNAH11 NM_001277115.2 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:9
• Conservation: PhyloP100: -1.49
• Publications: 18 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 -19 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.39).
• BP6: Variant 7-21899414-C-A is Benign according to our data. Variant chr7-21899414-C-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 178739.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-1.49 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.312 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.13128C>A	p.Leu4376Leu	synonymous	Exon 80 of 82	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.13128C>A	p.Leu4376Leu	synonymous	Exon 80 of 82	ENSP00000475939.1	Q96DT5
	DNAH11	ENST00000479878.1	TSL:3	n.499C>A		non_coding_transcript_exon	Exon 3 of 5

Frequencies

GnomAD3 genomes AF: 0.247 AC: 37512 AN: 151982 Hom.: 5451 Cov.: 32

Gnomad AFR AF: 0.102

Gnomad AMI AF: 0.202

Gnomad AMR AF: 0.275

Gnomad ASJ AF: 0.393

Gnomad EAS AF: 0.161

Gnomad SAS AF: 0.227

Gnomad FIN AF: 0.331

Gnomad MID AF: 0.266

Gnomad NFE AF: 0.316

Gnomad OTH AF: 0.266

GnomAD2 exomes AF: 0.277 AC: 68923 AN: 248912 AF XY: 0.282

Gnomad AFR exome AF: 0.0950

Gnomad AMR exome AF: 0.253

Gnomad ASJ exome AF: 0.391

Gnomad EAS exome AF: 0.168

Gnomad FIN exome AF: 0.318

Gnomad NFE exome AF: 0.316

Gnomad OTH exome AF: 0.294

GnomAD4 exome AF: 0.302 AC: 441599 AN: 1461174 Hom.: 68815 Cov.: 35 AF XY: 0.301 AC XY: 218598 AN XY: 726912

African (AFR) AF: 0.0929 AC: 3110 AN: 33478

American (AMR) AF: 0.259 AC: 11565 AN: 44718

Ashkenazi Jewish (ASJ) AF: 0.387 AC: 10118 AN: 26124

East Asian (EAS) AF: 0.166 AC: 6581 AN: 39698

South Asian (SAS) AF: 0.244 AC: 21040 AN: 86248

European-Finnish (FIN) AF: 0.322 AC: 17167 AN: 53384

Middle Eastern (MID) AF: 0.308 AC: 1774 AN: 5766

European-Non Finnish (NFE) AF: 0.317 AC: 352575 AN: 1111402

Other (OTH) AF: 0.293 AC: 17669 AN: 60356

GnomAD4 genome AF: 0.247 AC: 37499 AN: 152102 Hom.: 5447 Cov.: 32 AF XY: 0.247 AC XY: 18339 AN XY: 74316

African (AFR) AF: 0.102 AC: 4240 AN: 41524

American (AMR) AF: 0.274 AC: 4189 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.393 AC: 1365 AN: 3470

East Asian (EAS) AF: 0.161 AC: 829 AN: 5162

South Asian (SAS) AF: 0.227 AC: 1095 AN: 4820

European-Finnish (FIN) AF: 0.331 AC: 3498 AN: 10554

Middle Eastern (MID) AF: 0.259 AC: 76 AN: 294

European-Non Finnish (NFE) AF: 0.316 AC: 21466 AN: 67968

Other (OTH) AF: 0.264 AC: 557 AN: 2110

Alfa AF: 0.286 Hom.: 16593

Bravo AF: 0.236

Asia WGS AF: 0.184 AC: 641 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	4	not specified (4)
-	-	2	not provided (2)
-	-	2	Primary ciliary dyskinesia (2)
-	-	1	Primary ciliary dyskinesia 7 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.39
CADD	Benign	0.21
DANN	Benign	0.87
PhyloP100		-1.5
Mutation Taster		=99/1	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs56333627; hg19: chr7-21939032; COSMIC: COSV60940598; COSMIC: COSV60940598;