rs368331

chr7-21703356-A-Gchr7-21703356-A-T

Variant summary

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

The NM_001277115.2(DNAH11):c.6273+554A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0483 in 155,720 control chromosomes in the GnomAD database, including 269 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 0.048 (260 hom., cov: 32)
  • Exomes 𝑓: 0.055 (9 hom.)
• Consequence: DNAH11 NM_001277115.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.169

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=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.135 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DNAH11	NM_001277115.2	c.6273+554A>G		intron_variant		ENST00000409508.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DNAH11	ENST00000409508.8	c.6273+554A>G		intron_variant		5	NM_001277115.2	P1
DNAH11	ENST00000465129.1	n.94-93A>G		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.0482 AC: 7335 AN: 152148 Hom.: 262 Cov.: 32

Gnomad AFR AF: 0.0109

Gnomad AMI AF: 0.115

Gnomad AMR AF: 0.0245

Gnomad ASJ AF: 0.0490

Gnomad EAS AF: 0.143

Gnomad SAS AF: 0.0828

Gnomad FIN AF: 0.0603

Gnomad MID AF: 0.0411

Gnomad NFE AF: 0.0635

Gnomad OTH AF: 0.0565

GnomAD4 exome AF: 0.0553 AC: 191 AN: 3454 Hom.: 9 AF XY: 0.0629 AC XY: 115 AN XY: 1828

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0278

Gnomad4 ASJ exome AF: 0.0556

Gnomad4 EAS exome AF: 0.0667

Gnomad4 SAS exome AF: 0.0822

Gnomad4 FIN exome AF: 0.0652

Gnomad4 NFE exome AF: 0.0538

Gnomad4 OTH exome AF: 0.0654

GnomAD4 genome AF: 0.0482 AC: 7333 AN: 152266 Hom.: 260 Cov.: 32 AF XY: 0.0484 AC XY: 3606 AN XY: 74466

Gnomad4 AFR AF: 0.0108

Gnomad4 AMR AF: 0.0245

Gnomad4 ASJ AF: 0.0490

Gnomad4 EAS AF: 0.144

Gnomad4 SAS AF: 0.0831

Gnomad4 FIN AF: 0.0603

Gnomad4 NFE AF: 0.0635

Gnomad4 OTH AF: 0.0554

Alfa AF: 0.0599 Hom.: 659

Bravo AF: 0.0443

Asia WGS AF: 0.0910 AC: 316 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
Cadd	Benign	0.37
Dann	Benign	0.54

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: rs368331; hg19: chr7-21742974;