rs2072221

Variant names:

• chr7-21735825-G-A
• rs2072221
• NM_001277115.2:c.7626G>A

Your query was ambiguous. Multiple possible variants found:

• chr7-21735825-G-A
• chr7-21735825-G-C
• chr7-21735825-G-T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_001277115.2(DNAH11):​c.7626G>A​(p.Thr2542Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.855 in 1,610,410 control chromosomes in the GnomAD database, including 592,010 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Synonymous variant affecting the same amino acid position (i.e. T2542T) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.83 (53172 hom., cov: 32)
  • Exomes 𝑓: 0.86 (538838 hom.)
• Consequence: DNAH11 NM_001277115.2 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:8
• Conservation: PhyloP100: -0.496
• 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: 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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.67).
• BP6: Variant 7-21735825-G-A is Benign according to our data. Variant chr7-21735825-G-A is described in ClinVar as Benign. ClinVar VariationId is 163110.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.496 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.863 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.7626G>A	p.Thr2542Thr	synonymous	Exon 46 of 82	NP_001264044.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAH11	ENST00000409508.8	TSL:5 MANE Select	c.7626G>A	p.Thr2542Thr	synonymous	Exon 46 of 82	ENSP00000475939.1
	DNAH11	ENST00000605912.1	TSL:3	c.186G>A	p.Thr62Thr	synonymous	Exon 1 of 4	ENSP00000476068.1

Frequencies

GnomAD3 genomes AF: 0.833 AC: 126621 AN: 152026 Hom.: 53154 Cov.: 32

Gnomad AFR AF: 0.795

Gnomad AMI AF: 0.863

Gnomad AMR AF: 0.868

Gnomad ASJ AF: 0.769

Gnomad EAS AF: 0.527

Gnomad SAS AF: 0.761

Gnomad FIN AF: 0.904

Gnomad MID AF: 0.797

Gnomad NFE AF: 0.869

Gnomad OTH AF: 0.817

GnomAD2 exomes AF: 0.825 AC: 204412 AN: 247696 AF XY: 0.827

Gnomad AFR exome AF: 0.796

Gnomad AMR exome AF: 0.865

Gnomad ASJ exome AF: 0.777

Gnomad EAS exome AF: 0.519

Gnomad FIN exome AF: 0.900

Gnomad NFE exome AF: 0.867

Gnomad OTH exome AF: 0.828

GnomAD4 exome AF: 0.857 AC: 1250264 AN: 1458266 Hom.: 538838 Cov.: 47 AF XY: 0.856 AC XY: 620240 AN XY: 724930

African (AFR) AF: 0.794 AC: 26506 AN: 33386

American (AMR) AF: 0.867 AC: 38652 AN: 44586

Ashkenazi Jewish (ASJ) AF: 0.775 AC: 20183 AN: 26044

East Asian (EAS) AF: 0.566 AC: 22428 AN: 39624

South Asian (SAS) AF: 0.790 AC: 67727 AN: 85732

European-Finnish (FIN) AF: 0.897 AC: 47786 AN: 53298

Middle Eastern (MID) AF: 0.771 AC: 4434 AN: 5752

European-Non Finnish (NFE) AF: 0.877 AC: 972675 AN: 1109624

Other (OTH) AF: 0.828 AC: 49873 AN: 60220

GnomAD4 genome AF: 0.833 AC: 126695 AN: 152144 Hom.: 53172 Cov.: 32 AF XY: 0.832 AC XY: 61855 AN XY: 74360

African (AFR) AF: 0.795 AC: 32988 AN: 41494

American (AMR) AF: 0.868 AC: 13264 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.769 AC: 2671 AN: 3472

East Asian (EAS) AF: 0.527 AC: 2718 AN: 5156

South Asian (SAS) AF: 0.760 AC: 3662 AN: 4816

European-Finnish (FIN) AF: 0.904 AC: 9571 AN: 10586

Middle Eastern (MID) AF: 0.789 AC: 232 AN: 294

European-Non Finnish (NFE) AF: 0.869 AC: 59082 AN: 68016

Other (OTH) AF: 0.815 AC: 1722 AN: 2114

Alfa AF: 0.854 Hom.: 143290

Bravo AF: 0.839

ClinVar

ClinVar submissions as Germline

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	-0.67
CADD	Benign	0.13
DANN	Benign	0.43
PhyloP100		-0.50
PromoterAI		-0.019	Neutral
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: rs2072221; hg19: chr7-21775443; COSMIC: COSV60961001;