rs4722067

Variant names:

• chr7-21861948-T-C
• rs4722067
• NM_001277115.2:c.11298T>C

Your query was ambiguous. Multiple possible variants found:

• chr7-21861948-T-C
• chr7-21861948-T-A
• chr7-21861948-T-G

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BA1

The NM_001277115.2(DNAH11):​c.11298T>C​(p.His3766His) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.779 in 1,613,306 control chromosomes in the GnomAD database, including 496,202 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.72 (40341 hom., cov: 30)
  • Exomes 𝑓: 0.79 (455861 hom.)
• Consequence: DNAH11 NM_001277115.2 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:8
• Conservation: PhyloP100: -2.36
• Publications: 19 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 -19 ACMG points.

• BP4: Computational evidence support a benign effect (REVEL=0.135).
• BP6: Variant 7-21861948-T-C is Benign according to our data. Variant chr7-21861948-T-C is described in ClinVar as Benign. ClinVar VariationId is 163126.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-2.36 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.808 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.11298T>C	p.His3766His	synonymous	Exon 69 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.11298T>C	p.His3766His	synonymous	Exon 69 of 82	ENSP00000475939.1	Q96DT5
	DNAH11	ENST00000421290.1	TSL:4	n.481T>C		non_coding_transcript_exon	Exon 4 of 4
	DNAH11	ENST00000607413.5	TSL:4	n.561T>C		non_coding_transcript_exon	Exon 4 of 4

Frequencies

GnomAD3 genomes AF: 0.720 AC: 109280 AN: 151842 Hom.: 40296 Cov.: 30

Gnomad AFR AF: 0.590

Gnomad AMI AF: 0.877

Gnomad AMR AF: 0.655

Gnomad ASJ AF: 0.827

Gnomad EAS AF: 0.543

Gnomad SAS AF: 0.662

Gnomad FIN AF: 0.771

Gnomad MID AF: 0.741

Gnomad NFE AF: 0.814

Gnomad OTH AF: 0.744

GnomAD2 exomes AF: 0.721 AC: 179230 AN: 248552 AF XY: 0.731

Gnomad AFR exome AF: 0.586

Gnomad AMR exome AF: 0.569

Gnomad ASJ exome AF: 0.816

Gnomad EAS exome AF: 0.541

Gnomad FIN exome AF: 0.760

Gnomad NFE exome AF: 0.811

Gnomad OTH exome AF: 0.752

GnomAD4 exome AF: 0.786 AC: 1148072 AN: 1461346 Hom.: 455861 Cov.: 52 AF XY: 0.784 AC XY: 569803 AN XY: 726950

African (AFR) AF: 0.587 AC: 19630 AN: 33462

American (AMR) AF: 0.580 AC: 25937 AN: 44684

Ashkenazi Jewish (ASJ) AF: 0.813 AC: 21256 AN: 26134

East Asian (EAS) AF: 0.536 AC: 21273 AN: 39674

South Asian (SAS) AF: 0.674 AC: 58057 AN: 86174

European-Finnish (FIN) AF: 0.761 AC: 40628 AN: 53372

Middle Eastern (MID) AF: 0.757 AC: 4359 AN: 5760

European-Non Finnish (NFE) AF: 0.819 AC: 910463 AN: 1111724

Other (OTH) AF: 0.770 AC: 46469 AN: 60362

GnomAD4 genome AF: 0.720 AC: 109375 AN: 151960 Hom.: 40341 Cov.: 30 AF XY: 0.716 AC XY: 53141 AN XY: 74268

African (AFR) AF: 0.591 AC: 24472 AN: 41420

American (AMR) AF: 0.654 AC: 9997 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.827 AC: 2868 AN: 3468

East Asian (EAS) AF: 0.542 AC: 2793 AN: 5152

South Asian (SAS) AF: 0.662 AC: 3179 AN: 4800

European-Finnish (FIN) AF: 0.771 AC: 8130 AN: 10542

Middle Eastern (MID) AF: 0.738 AC: 217 AN: 294

European-Non Finnish (NFE) AF: 0.814 AC: 55345 AN: 67978

Other (OTH) AF: 0.745 AC: 1574 AN: 2112

Alfa AF: 0.774 Hom.: 150638

Bravo AF: 0.705

Asia WGS AF: 0.615 AC: 2140 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	-0.80
CADD	Benign	0.0070
DANN	Benign	0.29
PhyloP100		-2.4
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs4722067; hg19: chr7-21901566; COSMIC: COSV60954482;