7-21567734-T-C

Variant names:

• chr7-21567734-T-C
• rs12670798
• NM_001277115.2:c.1195-2335T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001277115.2(DNAH11):​c.1195-2335T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.262 in 152,184 control chromosomes in the GnomAD database, including 5,626 homozygotes. 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 0.26 (5626 hom., cov: 33)
• Consequence: DNAH11 NM_001277115.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.18
• Publications: 90 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

LOC105375183 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.502 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNAH11	NM_001277115.2	c.1195-2335T>C		intron_variant	Intron 6 of 81	ENST00000409508.8	NP_001264044.1
LOC105375183	XR_007060247.1	n.282+5592A>G		intron_variant	Intron 3 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DNAH11	ENST00000409508.8	c.1195-2335T>C		intron_variant	Intron 6 of 81	5	NM_001277115.2	ENSP00000475939.1
DNAH11	ENST00000496218.1	n.81-2335T>C		intron_variant	Intron 1 of 1	2

Frequencies

GnomAD3 genomes AF: 0.262 AC: 39886 AN: 152066 Hom.: 5614 Cov.: 33

Gnomad AFR AF: 0.324

Gnomad AMI AF: 0.121

Gnomad AMR AF: 0.199

Gnomad ASJ AF: 0.138

Gnomad EAS AF: 0.519

Gnomad SAS AF: 0.250

Gnomad FIN AF: 0.235

Gnomad MID AF: 0.168

Gnomad NFE AF: 0.234

Gnomad OTH AF: 0.238

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.262 AC: 39945 AN: 152184 Hom.: 5626 Cov.: 33 AF XY: 0.261 AC XY: 19440 AN XY: 74406

African (AFR) AF: 0.324 AC: 13461 AN: 41512

American (AMR) AF: 0.199 AC: 3039 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.138 AC: 478 AN: 3470

East Asian (EAS) AF: 0.518 AC: 2684 AN: 5178

South Asian (SAS) AF: 0.251 AC: 1209 AN: 4822

European-Finnish (FIN) AF: 0.235 AC: 2484 AN: 10586

Middle Eastern (MID) AF: 0.170 AC: 50 AN: 294

European-Non Finnish (NFE) AF: 0.234 AC: 15924 AN: 68010

Other (OTH) AF: 0.240 AC: 506 AN: 2112

Alfa AF: 0.248 Hom.: 16523

Bravo AF: 0.263

Asia WGS AF: 0.397 AC: 1382 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	2.5
DANN	Benign	0.43
PhyloP100		-1.2
Mutation Taster		=100/0	polymorphism (auto)

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: rs12670798; hg19: chr7-21607352;