rs72657379

Variant names:

• chr7-21779056-G-A
• rs72657379
• NM_001277115.2:c.9435G>A

Your query was ambiguous. Multiple possible variants found:

• chr7-21779056-G-A
• chr7-21779056-G-C
• chr7-21779056-G-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Moderate BP6 BP7 BS1 BS2

The NM_001277115.2(DNAH11):​c.9435G>A​(p.Thr3145Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00682 in 1,613,338 control chromosomes in the GnomAD database, including 59 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

• Frequency:
  • Genomes: 𝑓 0.0043 (3 hom., cov: 32)
  • Exomes 𝑓: 0.0071 (56 hom.)
• Consequence: DNAH11 NM_001277115.2 synonymous
• Clinical Significance: Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1 B:5
• Conservation: PhyloP100: -0.689
• Publications: 5 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.38).
• BP6: Variant 7-21779056-G-A is Benign according to our data. Variant chr7-21779056-G-A is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 226590.
• BP7: Synonymous conserved (PhyloP=-0.689 with no splicing effect.
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.00428 (652/152284) while in subpopulation NFE AF = 0.00782 (532/68022). AF 95% confidence interval is 0.00727. There are 3 homozygotes in GnomAd4. There are 270 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 3 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAH11	NM_001277115.2	MANE Select	c.9435G>A	p.Thr3145Thr	synonymous	Exon 57 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.9435G>A	p.Thr3145Thr	synonymous	Exon 57 of 82	ENSP00000475939.1

Frequencies

GnomAD3 genomes AF: 0.00428 AC: 652 AN: 152166 Hom.: 3 Cov.: 32

Gnomad AFR AF: 0.00154

Gnomad AMI AF: 0.00439

Gnomad AMR AF: 0.00164

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000385

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00160

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.00782

Gnomad OTH AF: 0.00239

GnomAD2 exomes AF: 0.00391 AC: 971 AN: 248558 AF XY: 0.00381

Gnomad AFR exome AF: 0.00103

Gnomad AMR exome AF: 0.000931

Gnomad ASJ exome AF: 0.0000995

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00255

Gnomad NFE exome AF: 0.00744

Gnomad OTH exome AF: 0.00266

GnomAD4 exome AF: 0.00708 AC: 10351 AN: 1461054 Hom.: 56 Cov.: 31 AF XY: 0.00692 AC XY: 5031 AN XY: 726762

African (AFR) AF: 0.00126 AC: 42 AN: 33454

American (AMR) AF: 0.000940 AC: 42 AN: 44670

Ashkenazi Jewish (ASJ) AF: 0.000153 AC: 4 AN: 26116

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39644

South Asian (SAS) AF: 0.000476 AC: 41 AN: 86208

European-Finnish (FIN) AF: 0.00251 AC: 134 AN: 53392

Middle Eastern (MID) AF: 0.000696 AC: 4 AN: 5748

European-Non Finnish (NFE) AF: 0.00883 AC: 9814 AN: 1111482

Other (OTH) AF: 0.00446 AC: 269 AN: 60340

GnomAD4 genome AF: 0.00428 AC: 652 AN: 152284 Hom.: 3 Cov.: 32 AF XY: 0.00363 AC XY: 270 AN XY: 74472

African (AFR) AF: 0.00154 AC: 64 AN: 41552

American (AMR) AF: 0.00163 AC: 25 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.000386 AC: 2 AN: 5180

South Asian (SAS) AF: 0.000414 AC: 2 AN: 4830

European-Finnish (FIN) AF: 0.00160 AC: 17 AN: 10614

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.00782 AC: 532 AN: 68022

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

Alfa AF: 0.00625 Hom.: 13

Bravo AF: 0.00390

ClinVar

ClinVar submissions as Germline

Significance: Conflicting classifications of pathogenicity

Revision: criteria provided, conflicting classifications

Pathogenic	VUS	Benign	Condition
-	-	2	not specified (2)
-	1	1	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	-0.38
CADD	Benign	1.9
DANN	Benign	0.70
PhyloP100		-0.69
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs72657379; hg19: chr7-21818674;