7-21765597-G-C

Variant names:

• chr7-21765597-G-C
• rs72657374
• NM_001277115.2:c.9102+8G>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001277115.2(DNAH11):​c.9102+8G>C variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000691 in 144,634 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.0000069 (0 hom., cov: 31)
• Consequence: DNAH11 NM_001277115.2 splice_region, intron
• Scores: Splicing: ADA: 0.0001451
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.150
• Publications: 2 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.71).

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.9102+8G>C		splice_region intron	N/A	NP_001264044.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAH11	ENST00000409508.8	TSL:5 MANE Select	c.9102+8G>C		splice_region intron	N/A	ENSP00000475939.1

Frequencies

GnomAD3 genomes AF: 0.00000691 AC: 1 AN: 144634 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.0000255

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: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 32

GnomAD4 genome AF: 0.00000691 AC: 1 AN: 144634 Hom.: 0 Cov.: 31 AF XY: 0.0000143 AC XY: 1 AN XY: 70122

African (AFR) AF: 0.0000255 AC: 1 AN: 39268

American (AMR) AF: 0.00 AC: 0 AN: 13762

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3422

East Asian (EAS) AF: 0.00 AC: 0 AN: 4934

South Asian (SAS) AF: 0.00 AC: 0 AN: 4394

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 9610

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 304

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 66102

Other (OTH) AF: 0.00 AC: 0 AN: 1952

Alfa AF: 0.00 Hom.: 6

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.71
CADD	Benign	0.55
DANN	Benign	0.64
PhyloP100		-0.15

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00015
dbscSNV1_RF	Benign	0.0080
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: rs72657374; hg19: chr7-21805215;