7-21606637-C-G

Variant names:

• chr7-21606637-C-G
• rs886038464
• NM_001277115.2:c.3766-10C>G

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001277115.2(DNAH11):​c.3766-10C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.000029 (0 hom., cov: 16)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: DNAH11 NM_001277115.2 intron
• Scores: Splicing: ADA: 0.0002925
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.752
• 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), Laboratory for Molecular Medicine, ClinGen
• primary ciliary dyskinesia

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).

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.3766-10C>G		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.3766-10C>G		intron	N/A	ENSP00000475939.1	Q96DT5

Frequencies

GnomAD3 genomes AF: 0.0000294 AC: 2 AN: 68008 Hom.: 0 Cov.: 16

Gnomad AFR AF: 0.0000607

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000287

Gnomad OTH AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 749662 Hom.: 0 Cov.: 24 AF XY: 0.00 AC XY: 0 AN XY: 377646

African (AFR) AF: 0.00 AC: 0 AN: 17810

American (AMR) AF: 0.00 AC: 0 AN: 18522

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 14984

East Asian (EAS) AF: 0.00 AC: 0 AN: 26470

South Asian (SAS) AF: 0.00 AC: 0 AN: 48000

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 32518

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2594

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 554316

Other (OTH) AF: 0.00 AC: 0 AN: 34448

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000294 AC: 2 AN: 68050 Hom.: 0 Cov.: 16 AF XY: 0.0000629 AC XY: 2 AN XY: 31792

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.0000605 AC: 1 AN: 16536

American (AMR) AF: 0.00 AC: 0 AN: 5980

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2016

East Asian (EAS) AF: 0.00 AC: 0 AN: 1936

South Asian (SAS) AF: 0.00 AC: 0 AN: 2362

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 2938

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 84

European-Non Finnish (NFE) AF: 0.0000287 AC: 1 AN: 34880

Other (OTH) AF: 0.00 AC: 0 AN: 850

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.046
DANN	Benign	0.26
PhyloP100		-0.75

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00029
dbscSNV1_RF	Benign	0.026
SpliceAI score (max)		0.15		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs886038464;

hg19: chr7-21646255;