rs10485974

chr7-21714988-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_001277115.2(DNAH11):c.6984-2787G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0104 in 152,250 control chromosomes in the GnomAD database, including 15 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 0.010 (15 hom., cov: 32)
• Consequence: DNAH11 NM_001277115.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.17

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=-0.92).
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0104 (1576/152250) while in subpopulation AFR AF= 0.0212 (881/41538). AF 95% confidence interval is 0.02. There are 15 homozygotes in gnomad4. There are 756 alleles in male gnomad4 subpopulation. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 15 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DNAH11	NM_001277115.2	c.6984-2787G>C		intron_variant		ENST00000409508.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DNAH11	ENST00000409508.8	c.6984-2787G>C		intron_variant		5	NM_001277115.2	P1

Frequencies

GnomAD3 genomes AF: 0.0104 AC: 1578 AN: 152132 Hom.: 15 Cov.: 32

Gnomad AFR AF: 0.0213

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00819

Gnomad ASJ AF: 0.0288

Gnomad EAS AF: 0.00154

Gnomad SAS AF: 0.00290

Gnomad FIN AF: 0.00104

Gnomad MID AF: 0.00955

Gnomad NFE AF: 0.00600

Gnomad OTH AF: 0.0129

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

GnomAD4 genome AF: 0.0104 AC: 1576 AN: 152250 Hom.: 15 Cov.: 32 AF XY: 0.0102 AC XY: 756 AN XY: 74448

Gnomad4 AFR AF: 0.0212

Gnomad4 AMR AF: 0.00818

Gnomad4 ASJ AF: 0.0288

Gnomad4 EAS AF: 0.00135

Gnomad4 SAS AF: 0.00290

Gnomad4 FIN AF: 0.00104

Gnomad4 NFE AF: 0.00600

Gnomad4 OTH AF: 0.0128

Alfa AF: 0.00821 Hom.: 2

Bravo AF: 0.0112

Asia WGS AF: 0.0100 AC: 35 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
Cadd	Benign	0.15
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: rs10485974; hg19: chr7-21754606;