rs72658814

Variant names:

• chr7-21867972-C-T
• rs72658814
• NM_001277115.2:c.11804C>T

Your query was ambiguous. Multiple possible variants found:

• chr7-21867972-C-T
• chr7-21867972-C-G

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS2

The NM_001277115.2(DNAH11):​c.11804C>T​(p.Pro3935Leu) variant causes a missense change. The variant allele was found at a frequency of 0.000313 in 1,561,636 control chromosomes in the GnomAD database, including 2 homozygotes. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Synonymous variant affecting the same amino acid position (i.e. P3935P) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.00026 (0 hom., cov: 30)
  • Exomes 𝑓: 0.00032 (2 hom.)
• Consequence: DNAH11 NM_001277115.2 missense
• Clinical Significance: Conflicting classifications of pathogenicity criteria provided, conflicting classifications P:2 U:6 B:1
• Conservation: PhyloP100: 6.12
• Publications: 6 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: Likely_benign. The variant received -4 ACMG points.

• BS2: High Homozygotes in GnomAdExome4 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.11804C>T	p.Pro3935Leu	missense	Exon 72 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.11804C>T	p.Pro3935Leu	missense	Exon 72 of 82	ENSP00000475939.1	Q96DT5

Frequencies

GnomAD3 genomes AF: 0.000263 AC: 40 AN: 152066 Hom.: 0 Cov.: 30

Gnomad AFR AF: 0.000121

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000655

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000578

Gnomad SAS AF: 0.000416

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000426

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000327 AC: 57 AN: 174318 AF XY: 0.000315

Gnomad AFR exome AF: 0.000205

Gnomad AMR exome AF: 0.000268

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000555

Gnomad FIN exome AF: 0.000113

Gnomad NFE exome AF: 0.000489

Gnomad OTH exome AF: 0.000645

GnomAD4 exome AF: 0.000319 AC: 449 AN: 1409454 Hom.: 2 Cov.: 35 AF XY: 0.000322 AC XY: 224 AN XY: 696162

African (AFR) AF: 0.0000622 AC: 2 AN: 32150

American (AMR) AF: 0.000345 AC: 13 AN: 37684

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25182

East Asian (EAS) AF: 0.000539 AC: 20 AN: 37074

South Asian (SAS) AF: 0.0000883 AC: 7 AN: 79236

European-Finnish (FIN) AF: 0.000120 AC: 6 AN: 50182

Middle Eastern (MID) AF: 0.000176 AC: 1 AN: 5682

European-Non Finnish (NFE) AF: 0.000353 AC: 383 AN: 1083816

Other (OTH) AF: 0.000291 AC: 17 AN: 58448

GnomAD4 genome AF: 0.000263 AC: 40 AN: 152182 Hom.: 0 Cov.: 30 AF XY: 0.000215 AC XY: 16 AN XY: 74402

African (AFR) AF: 0.000120 AC: 5 AN: 41542

American (AMR) AF: 0.0000654 AC: 1 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.000580 AC: 3 AN: 5176

South Asian (SAS) AF: 0.000416 AC: 2 AN: 4806

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10596

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

European-Non Finnish (NFE) AF: 0.000427 AC: 29 AN: 67994

Other (OTH) AF: 0.00 AC: 0 AN: 2106

Alfa AF: 0.000420 Hom.: 0

Bravo AF: 0.000261

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000122 AC: 1

ExAC AF: 0.000262 AC: 31

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

ClinVar submissions

Significance: Conflicting classifications of pathogenicity

Revision: criteria provided, conflicting classifications

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.12
CADD	Uncertain	25
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.37	T
Eigen	Pathogenic	0.77
Eigen_PC	Pathogenic	0.78
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Pathogenic	0.99	D
M_CAP	Benign	0.068	D
MetaRNN	Uncertain	0.53	D
MetaSVM	Benign	-0.99	T
PhyloP100		6.1
PrimateAI	Uncertain	0.70	T
PROVEAN	Pathogenic	-8.7	D
REVEL	Uncertain	0.38
Sift	Uncertain	0.0010	D
Vest4		0.94
MVP		0.42
ClinPred		0.36	T
GERP RS		6.1
Varity_R		0.72
gMVP		0.63
Mutation Taster		=18/82	disease causing

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: rs72658814; hg19: chr7-21907590; COSMIC: COSV60990851;