7-21567734-T-C

Variant summary

Our verdict is Benign. Variant got -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

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]

LOC105375183 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	UniProt
DNAH11	NM_001277115.2	c.1195-2335T>C		intron_variant		ENST00000409508.8
LOC105375183	XR_007060247.1	n.282+5592A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DNAH11	ENST00000409508.8	c.1195-2335T>C		intron_variant		5	NM_001277115.2	P1
DNAH11	ENST00000496218.1	n.81-2335T>C		intron_variant, non_coding_transcript_variant		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

Gnomad4 AFR AF: 0.324

Gnomad4 AMR AF: 0.199

Gnomad4 ASJ AF: 0.138

Gnomad4 EAS AF: 0.518

Gnomad4 SAS AF: 0.251

Gnomad4 FIN AF: 0.235

Gnomad4 NFE AF: 0.234

Gnomad4 OTH AF: 0.240

Alfa AF: 0.245 Hom.: 7400

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

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

Publications

LitVar

Other links and lift over

dbSNP: rs12670798; hg19: chr7-21607352;