chr7-21738831-C-T

Variant names:

• chr7-21738831-C-T
• rs1109806
• NM_001277115.2:c.7776C>T

Variant summary

Our verdict is Benign. The variant received -18 ACMG points: 0P and 18B. BP4_Moderate BP6_Very_Strong BA1

The NM_001277115.2(DNAH11):​c.7776C>T​(p.His2592His) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.67 in 1,603,266 control chromosomes in the GnomAD database, including 366,485 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.64 (31924 hom., cov: 30)
  • Exomes 𝑓: 0.67 (334561 hom.)
• Consequence: DNAH11 NM_001277115.2 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:8
• Conservation: PhyloP100: 0.457
• Publications: 20 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: Labcorp Genetics (formerly Invitae), ClinGen, Laboratory for Molecular Medicine
• primary ciliary dyskinesia

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -18 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.43).
• BP6: Variant 7-21738831-C-T is Benign according to our data. Variant chr7-21738831-C-T is described in ClinVar as Benign. ClinVar VariationId is 163112.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.693 is higher than 0.05.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAH11	NM_001277115.2	MANE Select	c.7776C>T	p.His2592His	synonymous	Exon 47 of 82	NP_001264044.1	Q96DT5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAH11	ENST00000409508.8	TSL:5 MANE Select	c.7776C>T	p.His2592His	synonymous	Exon 47 of 82	ENSP00000475939.1	Q96DT5
	DNAH11	ENST00000605912.1	TSL:3	c.336C>T	p.His112His	synonymous	Exon 2 of 4	ENSP00000476068.1	U3KQN2

Frequencies

GnomAD3 genomes AF: 0.641 AC: 97336 AN: 151746 Hom.: 31899 Cov.: 30

Gnomad AFR AF: 0.607

Gnomad AMI AF: 0.770

Gnomad AMR AF: 0.600

Gnomad ASJ AF: 0.622

Gnomad EAS AF: 0.237

Gnomad SAS AF: 0.596

Gnomad FIN AF: 0.686

Gnomad MID AF: 0.563

Gnomad NFE AF: 0.698

Gnomad OTH AF: 0.640

GnomAD2 exomes AF: 0.612 AC: 144780 AN: 236554 AF XY: 0.621

Gnomad AFR exome AF: 0.599

Gnomad AMR exome AF: 0.511

Gnomad ASJ exome AF: 0.611

Gnomad EAS exome AF: 0.222

Gnomad FIN exome AF: 0.676

Gnomad NFE exome AF: 0.694

Gnomad OTH exome AF: 0.643

GnomAD4 exome AF: 0.673 AC: 976458 AN: 1451402 Hom.: 334561 Cov.: 48 AF XY: 0.672 AC XY: 484776 AN XY: 720924

African (AFR) AF: 0.617 AC: 20531 AN: 33254

American (AMR) AF: 0.521 AC: 22709 AN: 43594

Ashkenazi Jewish (ASJ) AF: 0.610 AC: 15815 AN: 25906

East Asian (EAS) AF: 0.224 AC: 8842 AN: 39464

South Asian (SAS) AF: 0.623 AC: 52113 AN: 83678

European-Finnish (FIN) AF: 0.676 AC: 35782 AN: 52900

Middle Eastern (MID) AF: 0.622 AC: 3578 AN: 5750

European-Non Finnish (NFE) AF: 0.703 AC: 778205 AN: 1106816

Other (OTH) AF: 0.648 AC: 38883 AN: 60040

GnomAD4 genome AF: 0.641 AC: 97398 AN: 151864 Hom.: 31924 Cov.: 30 AF XY: 0.636 AC XY: 47210 AN XY: 74228

African (AFR) AF: 0.608 AC: 25152 AN: 41398

American (AMR) AF: 0.599 AC: 9133 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.622 AC: 2160 AN: 3470

East Asian (EAS) AF: 0.236 AC: 1220 AN: 5160

South Asian (SAS) AF: 0.595 AC: 2859 AN: 4804

European-Finnish (FIN) AF: 0.686 AC: 7235 AN: 10546

Middle Eastern (MID) AF: 0.554 AC: 163 AN: 294

European-Non Finnish (NFE) AF: 0.698 AC: 47424 AN: 67918

Other (OTH) AF: 0.641 AC: 1354 AN: 2112

Alfa AF: 0.669 Hom.: 132715

Bravo AF: 0.628

Asia WGS AF: 0.453 AC: 1576 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	4	not specified (4)
-	-	2	Primary ciliary dyskinesia (2)
-	-	1	not provided (1)
-	-	1	Primary ciliary dyskinesia 7 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.43
CADD	Benign	2.3
DANN	Benign	0.32
PhyloP100		0.46
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs1109806; hg19: chr7-21778449; COSMIC: COSV60966411;