rs62445328

Variant names:

• chr7-21745031-C-T
• rs62445328
• NM_001277115.2:c.8478C>T

Your query was ambiguous. Multiple possible variants found:

• chr7-21745031-C-T
• chr7-21745031-C-G

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.8478C>T​(p.His2826His) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00648 in 1,609,286 control chromosomes in the GnomAD database, including 47 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 0.0039 (2 hom., cov: 33)
  • Exomes 𝑓: 0.0067 (45 hom.)
• Consequence: DNAH11 NM_001277115.2 synonymous
• Clinical Significance: Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1 B:5
• Conservation: PhyloP100: -0.182
• 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: 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.42).
• BP6: Variant 7-21745031-C-T is Benign according to our data. Variant chr7-21745031-C-T is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 220474.
• BP7: Synonymous conserved (PhyloP=-0.182 with no splicing effect.
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.00391 (596/152280) while in subpopulation NFE AF = 0.00687 (467/68010). AF 95% confidence interval is 0.00635. There are 2 homozygotes in GnomAd4. There are 298 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 2 AD,AR 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.8478C>T	p.His2826His	synonymous	Exon 51 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.8478C>T	p.His2826His	synonymous	Exon 51 of 82	ENSP00000475939.1	Q96DT5
	DNAH11	ENST00000605912.1	TSL:3	c.*112C>T		downstream_gene	N/A	ENSP00000476068.1	U3KQN2

Frequencies

GnomAD3 genomes AF: 0.00392 AC: 596 AN: 152162 Hom.: 2 Cov.: 33

Gnomad AFR AF: 0.00138

Gnomad AMI AF: 0.0241

Gnomad AMR AF: 0.00131

Gnomad ASJ AF: 0.00259

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00151

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00687

Gnomad OTH AF: 0.00239

GnomAD2 exomes AF: 0.00369 AC: 889 AN: 240852 AF XY: 0.00374

Gnomad AFR exome AF: 0.00108

Gnomad AMR exome AF: 0.000417

Gnomad ASJ exome AF: 0.00234

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00203

Gnomad NFE exome AF: 0.00707

Gnomad OTH exome AF: 0.00254

GnomAD4 exome AF: 0.00675 AC: 9828 AN: 1457006 Hom.: 45 Cov.: 31 AF XY: 0.00648 AC XY: 4689 AN XY: 724092

African (AFR) AF: 0.00135 AC: 45 AN: 33426

American (AMR) AF: 0.000499 AC: 22 AN: 44084

Ashkenazi Jewish (ASJ) AF: 0.00254 AC: 66 AN: 25984

East Asian (EAS) AF: 0.00 AC: 0 AN: 39570

South Asian (SAS) AF: 0.000176 AC: 15 AN: 84996

European-Finnish (FIN) AF: 0.00288 AC: 153 AN: 53196

Middle Eastern (MID) AF: 0.000174 AC: 1 AN: 5758

European-Non Finnish (NFE) AF: 0.00837 AC: 9292 AN: 1109748

Other (OTH) AF: 0.00388 AC: 234 AN: 60244

GnomAD4 genome AF: 0.00391 AC: 596 AN: 152280 Hom.: 2 Cov.: 33 AF XY: 0.00400 AC XY: 298 AN XY: 74452

African (AFR) AF: 0.00137 AC: 57 AN: 41556

American (AMR) AF: 0.00131 AC: 20 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.00259 AC: 9 AN: 3472

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

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00151 AC: 16 AN: 10616

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

European-Non Finnish (NFE) AF: 0.00687 AC: 467 AN: 68010

Other (OTH) AF: 0.00237 AC: 5 AN: 2112

Alfa AF: 0.00671 Hom.: 14

Bravo AF: 0.00420

ClinVar

ClinVar submissions

Significance: Conflicting classifications of pathogenicity

Revision: criteria provided, conflicting classifications

Pathogenic	VUS	Benign	Condition
-	1	2	Primary ciliary dyskinesia (3)
-	-	2	not specified (2)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.42
CADD	Benign	2.3
DANN	Benign	0.31
PhyloP100		-0.18
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: rs62445328; hg19: chr7-21784649;