rs116368970

Variant names:

• chr7-21801127-T-C
• rs116368970
• NM_001277115.2:c.10027-10T>C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_001277115.2(DNAH11):​c.10027-10T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000886 in 1,600,040 control chromosomes in the GnomAD database, including 12 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0042 (2 hom., cov: 32)
  • Exomes 𝑓: 0.00054 (10 hom.)
• Consequence: DNAH11 NM_001277115.2 intron
• Scores: Splicing: ADA: 0.0003970
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 0.810
• Publications: 1 publications found

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]

DNAH11 Gene-Disease associations (from GenCC):

• primary ciliary dyskinesia 7

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: PanelApp Australia, Laboratory for Molecular Medicine, Labcorp Genetics (formerly Invitae), ClinGen
• primary ciliary dyskinesia

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 7-21801127-T-C is Benign according to our data. Variant chr7-21801127-T-C is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 226578.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00419 (639/152330) while in subpopulation AFR AF = 0.0145 (602/41582). AF 95% confidence interval is 0.0135. There are 2 homozygotes in GnomAd4. There are 294 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 2 AR,AD gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001277115.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAH11	NM_001277115.2	MANE Select	c.10027-10T>C		intron	N/A	NP_001264044.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAH11	ENST00000409508.8	TSL:5 MANE Select	c.10027-10T>C		intron	N/A	ENSP00000475939.1

Frequencies

GnomAD3 genomes AF: 0.00418 AC: 637 AN: 152212 Hom.: 2 Cov.: 32

Gnomad AFR AF: 0.0145

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00144

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000147

Gnomad OTH AF: 0.00239

GnomAD2 exomes AF: 0.00122 AC: 279 AN: 227886 AF XY: 0.000937

Gnomad AFR exome AF: 0.0163

Gnomad AMR exome AF: 0.00112

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000886

Gnomad OTH exome AF: 0.00193

GnomAD4 exome AF: 0.000537 AC: 778 AN: 1447710 Hom.: 10 Cov.: 31 AF XY: 0.000477 AC XY: 343 AN XY: 718458

African (AFR) AF: 0.0166 AC: 551 AN: 33276

American (AMR) AF: 0.00136 AC: 58 AN: 42510

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25726

East Asian (EAS) AF: 0.00 AC: 0 AN: 39488

South Asian (SAS) AF: 0.0000239 AC: 2 AN: 83802

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52836

Middle Eastern (MID) AF: 0.000522 AC: 3 AN: 5746

European-Non Finnish (NFE) AF: 0.000109 AC: 120 AN: 1104340

Other (OTH) AF: 0.000734 AC: 44 AN: 59986

GnomAD4 genome AF: 0.00419 AC: 639 AN: 152330 Hom.: 2 Cov.: 32 AF XY: 0.00395 AC XY: 294 AN XY: 74488

African (AFR) AF: 0.0145 AC: 602 AN: 41582

American (AMR) AF: 0.00144 AC: 22 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10614

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000147 AC: 10 AN: 68022

Other (OTH) AF: 0.00237 AC: 5 AN: 2114

Alfa AF: 0.00255 Hom.: 1

Bravo AF: 0.00499

Asia WGS AF: 0.000577 AC: 2 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not specified (2)
-	-	2	Primary ciliary dyskinesia (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	9.4
DANN	Benign	0.28
PhyloP100		0.81
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00040
dbscSNV1_RF	Benign	0.070
SpliceAI score (max)		0.040		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs116368970; hg19: chr7-21840745;