rs2285947

Positions:

• chr7-21544470-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001277115.2(DNAH11):​c.352-536G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.443 in 151,966 control chromosomes in the GnomAD database, including 15,245 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 0.44 (15245 hom., cov: 32)
• Consequence: DNAH11 NM_001277115.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.119

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.484 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DNAH11	NM_001277115.2	c.352-536G>A		intron_variant		ENST00000409508.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DNAH11	ENST00000409508.8	c.352-536G>A		intron_variant		5	NM_001277115.2	P1
DNAH11	ENST00000607050.1	n.342-536G>A		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.443 AC: 67249 AN: 151848 Hom.: 15225 Cov.: 32

Gnomad AFR AF: 0.423

Gnomad AMI AF: 0.307

Gnomad AMR AF: 0.356

Gnomad ASJ AF: 0.476

Gnomad EAS AF: 0.262

Gnomad SAS AF: 0.488

Gnomad FIN AF: 0.416

Gnomad MID AF: 0.516

Gnomad NFE AF: 0.488

Gnomad OTH AF: 0.456

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

GnomAD4 genome AF: 0.443 AC: 67307 AN: 151966 Hom.: 15245 Cov.: 32 AF XY: 0.438 AC XY: 32571 AN XY: 74284

Gnomad4 AFR AF: 0.424

Gnomad4 AMR AF: 0.355

Gnomad4 ASJ AF: 0.476

Gnomad4 EAS AF: 0.263

Gnomad4 SAS AF: 0.489

Gnomad4 FIN AF: 0.416

Gnomad4 NFE AF: 0.488

Gnomad4 OTH AF: 0.452

Alfa AF: 0.467 Hom.: 5113

Bravo AF: 0.436

Asia WGS AF: 0.334 AC: 1160 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	2.8
DANN	Benign	0.42

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: rs2285947; hg19: chr7-21584088;