rs187489343

Variant names:

• chr7-21867973-G-A
• rs187489343
• NM_001277115.2:c.11805G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Moderate BP6 BP7 BS1 BS2

The NM_001277115.2(DNAH11):​c.11805G>A​(p.Pro3935Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000664 in 1,560,822 control chromosomes in the GnomAD database, including 13 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

• Frequency:
  • Genomes: 𝑓 0.0034 (8 hom., cov: 30)
  • Exomes 𝑓: 0.00036 (5 hom.)
• Consequence: DNAH11 NM_001277115.2 synonymous
• Clinical Significance: Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1 B:3
• Conservation: PhyloP100: -0.403
• 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: 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.43).
• BP6: Variant 7-21867973-G-A is Benign according to our data. Variant chr7-21867973-G-A is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 257857.
• BP7: Synonymous conserved (PhyloP=-0.403 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00344 (523/152196) while in subpopulation AFR AF = 0.0106 (441/41540). AF 95% confidence interval is 0.0098. There are 8 homozygotes in GnomAd4. There are 249 alleles in the male GnomAd4 subpopulation. Median coverage is 30. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 8 AD,AR 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.11805G>A	p.Pro3935Pro	synonymous	Exon 72 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.11805G>A	p.Pro3935Pro	synonymous	Exon 72 of 82	ENSP00000475939.1	Q96DT5

Frequencies

GnomAD3 genomes AF: 0.00344 AC: 523 AN: 152078 Hom.: 8 Cov.: 30

Gnomad AFR AF: 0.0106

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00433

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.000829

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00385

GnomAD2 exomes AF: 0.000913 AC: 158 AN: 173028 AF XY: 0.000809

Gnomad AFR exome AF: 0.0102

Gnomad AMR exome AF: 0.00108

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000141

Gnomad OTH exome AF: 0.000864

GnomAD4 exome AF: 0.000365 AC: 514 AN: 1408626 Hom.: 5 Cov.: 35 AF XY: 0.000362 AC XY: 252 AN XY: 695744

African (AFR) AF: 0.00990 AC: 318 AN: 32120

American (AMR) AF: 0.00136 AC: 51 AN: 37584

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25172

East Asian (EAS) AF: 0.000189 AC: 7 AN: 36986

South Asian (SAS) AF: 0.000847 AC: 67 AN: 79136

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50106

Middle Eastern (MID) AF: 0.000176 AC: 1 AN: 5676

European-Non Finnish (NFE) AF: 0.0000212 AC: 23 AN: 1083430

Other (OTH) AF: 0.000805 AC: 47 AN: 58416

GnomAD4 genome AF: 0.00344 AC: 523 AN: 152196 Hom.: 8 Cov.: 30 AF XY: 0.00335 AC XY: 249 AN XY: 74412

African (AFR) AF: 0.0106 AC: 441 AN: 41540

American (AMR) AF: 0.00432 AC: 66 AN: 15274

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

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5174

South Asian (SAS) AF: 0.000830 AC: 4 AN: 4820

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10602

Middle Eastern (MID) AF: 0.0102 AC: 3 AN: 294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68010

Other (OTH) AF: 0.00381 AC: 8 AN: 2102

Alfa AF: 0.00102 Hom.: 2

Bravo AF: 0.00399

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

ClinVar submissions

Significance: Conflicting classifications of pathogenicity

Revision: criteria provided, conflicting classifications

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.43
CADD	Benign	1.3
DANN	Benign	0.81
PhyloP100		-0.40
Mutation Taster		=89/11	polymorphism

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: rs187489343; hg19: chr7-21907591;