chr7-21821494-C-T

Position:

• chr7-21821494-C-T

Variant summary

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

The NM_001277115.2(DNAH11):​c.10691+3155C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.89 in 152,124 control chromosomes in the GnomAD database, including 60,458 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 0.89 (60458 hom., cov: 30)
• Consequence: DNAH11 NM_001277115.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.910

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=-1.06).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.915 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DNAH11	NM_001277115.2	c.10691+3155C>T		intron_variant		ENST00000409508.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DNAH11	ENST00000409508.8	c.10691+3155C>T		intron_variant		5	NM_001277115.2	P1

Frequencies

GnomAD3 genomes AF: 0.890 AC: 135357 AN: 152006 Hom.: 60437 Cov.: 30

Gnomad AFR AF: 0.833

Gnomad AMI AF: 0.923

Gnomad AMR AF: 0.906

Gnomad ASJ AF: 0.914

Gnomad EAS AF: 0.893

Gnomad SAS AF: 0.817

Gnomad FIN AF: 0.920

Gnomad MID AF: 0.924

Gnomad NFE AF: 0.921

Gnomad OTH AF: 0.899

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

GnomAD4 genome AF: 0.890 AC: 135431 AN: 152124 Hom.: 60458 Cov.: 30 AF XY: 0.890 AC XY: 66157 AN XY: 74372

Gnomad4 AFR AF: 0.832

Gnomad4 AMR AF: 0.906

Gnomad4 ASJ AF: 0.914

Gnomad4 EAS AF: 0.893

Gnomad4 SAS AF: 0.816

Gnomad4 FIN AF: 0.920

Gnomad4 NFE AF: 0.921

Gnomad4 OTH AF: 0.897

Alfa AF: 0.912 Hom.: 8518

Bravo AF: 0.889

Asia WGS AF: 0.848 AC: 2951 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.1
CADD	Benign	0.70
DANN	Benign	0.59

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: rs2390593; hg19: chr7-21861112;