rs755196801

Variant names:

• chr7-21867886-G-A
• rs755196801
• NM_001277115.2:c.11718G>A

Your query was ambiguous. Multiple possible variants found:

• chr7-21867886-G-A
• chr7-21867886-G-C
• chr7-21867886-G-T

Variant summary

Our verdict is Benign. The variant received -7 ACMG points: 0P and 7B. BP4_Strong BP6_Moderate BP7

The NM_001277115.2(DNAH11):​c.11718G>A​(p.Ala3906Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000418 in 1,578,296 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. A3906A) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.000046 (0 hom., cov: 30)
  • Exomes 𝑓: 0.000041 (0 hom.)
• Consequence: DNAH11 NM_001277115.2 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.28
• 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 -7 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BP6: Variant 7-21867886-G-A is Benign according to our data. Variant chr7-21867886-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 1113719.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-2.28 with no splicing effect.

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.11718G>A	p.Ala3906Ala	synonymous	Exon 72 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.11718G>A	p.Ala3906Ala	synonymous	Exon 72 of 82	ENSP00000475939.1

Frequencies

GnomAD3 genomes AF: 0.0000460 AC: 7 AN: 152032 Hom.: 0 Cov.: 30

Gnomad AFR AF: 0.0000242

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000772

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000294

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000961 AC: 19 AN: 197728 AF XY: 0.0000854

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000348

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00116

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.000195

GnomAD4 exome AF: 0.0000414 AC: 59 AN: 1426146 Hom.: 0 Cov.: 35 AF XY: 0.0000354 AC XY: 25 AN XY: 705848

African (AFR) AF: 0.00 AC: 0 AN: 32776

American (AMR) AF: 0.0000253 AC: 1 AN: 39514

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25520

East Asian (EAS) AF: 0.000652 AC: 25 AN: 38326

South Asian (SAS) AF: 0.0000493 AC: 4 AN: 81058

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51336

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5726

European-Non Finnish (NFE) AF: 0.0000146 AC: 16 AN: 1092752

Other (OTH) AF: 0.000220 AC: 13 AN: 59138

GnomAD4 genome AF: 0.0000460 AC: 7 AN: 152150 Hom.: 0 Cov.: 30 AF XY: 0.0000672 AC XY: 5 AN XY: 74380

African (AFR) AF: 0.0000241 AC: 1 AN: 41502

American (AMR) AF: 0.00 AC: 0 AN: 15266

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

East Asian (EAS) AF: 0.000773 AC: 4 AN: 5172

South Asian (SAS) AF: 0.00 AC: 0 AN: 4814

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10594

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000294 AC: 2 AN: 68012

Other (OTH) AF: 0.00 AC: 0 AN: 2114

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000945

Asia WGS AF: 0.000577 AC: 2 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	Primary ciliary dyskinesia (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	1.6
DANN	Benign	0.63
PhyloP100		-2.3
Mutation Taster		=92/8	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: rs755196801; hg19: chr7-21907504; COSMIC: COSV60949473;