rs62441683

Variant names:

• chr7-21588624-C-G
• rs62441683
• NM_001277115.2:c.1961C>G

Your query was ambiguous. Multiple possible variants found:

• chr7-21588624-C-G
• chr7-21588624-C-T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001277115.2(DNAH11):​c.1961C>G​(p.Ser654Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.148 in 1,609,436 control chromosomes in the GnomAD database, including 19,431 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S654F) has been classified as Benign.

• Frequency:
  • Genomes: 𝑓 0.11 (1279 hom., cov: 32)
  • Exomes 𝑓: 0.15 (18152 hom.)
• Consequence: DNAH11 NM_001277115.2 missense
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:8
• Conservation: PhyloP100: 1.78
• Publications: 18 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0017820597).
• BP6: Variant 7-21588624-C-G is Benign according to our data. Variant chr7-21588624-C-G is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 163098.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.164 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.1961C>G	p.Ser654Cys	missense	Exon 11 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.1961C>G	p.Ser654Cys	missense	Exon 11 of 82	ENSP00000475939.1	Q96DT5

Frequencies

GnomAD3 genomes AF: 0.114 AC: 17357 AN: 152108 Hom.: 1279 Cov.: 32

Gnomad AFR AF: 0.0292

Gnomad AMI AF: 0.0395

Gnomad AMR AF: 0.114

Gnomad ASJ AF: 0.187

Gnomad EAS AF: 0.0343

Gnomad SAS AF: 0.107

Gnomad FIN AF: 0.126

Gnomad MID AF: 0.174

Gnomad NFE AF: 0.167

Gnomad OTH AF: 0.140

GnomAD2 exomes AF: 0.124 AC: 30803 AN: 248726 AF XY: 0.129

Gnomad AFR exome AF: 0.0247

Gnomad AMR exome AF: 0.0751

Gnomad ASJ exome AF: 0.178

Gnomad EAS exome AF: 0.0309

Gnomad FIN exome AF: 0.119

Gnomad NFE exome AF: 0.165

Gnomad OTH exome AF: 0.140

GnomAD4 exome AF: 0.152 AC: 220923 AN: 1457210 Hom.: 18152 Cov.: 33 AF XY: 0.151 AC XY: 109822 AN XY: 725084

African (AFR) AF: 0.0234 AC: 781 AN: 33442

American (AMR) AF: 0.0803 AC: 3590 AN: 44690

Ashkenazi Jewish (ASJ) AF: 0.181 AC: 4714 AN: 26082

East Asian (EAS) AF: 0.0241 AC: 955 AN: 39664

South Asian (SAS) AF: 0.115 AC: 9926 AN: 86170

European-Finnish (FIN) AF: 0.121 AC: 6452 AN: 53292

Middle Eastern (MID) AF: 0.187 AC: 1074 AN: 5754

European-Non Finnish (NFE) AF: 0.167 AC: 184813 AN: 1107904

Other (OTH) AF: 0.143 AC: 8618 AN: 60212

GnomAD4 genome AF: 0.114 AC: 17355 AN: 152226 Hom.: 1279 Cov.: 32 AF XY: 0.111 AC XY: 8294 AN XY: 74426

African (AFR) AF: 0.0292 AC: 1212 AN: 41554

American (AMR) AF: 0.114 AC: 1738 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.187 AC: 648 AN: 3472

East Asian (EAS) AF: 0.0344 AC: 178 AN: 5172

South Asian (SAS) AF: 0.107 AC: 514 AN: 4812

European-Finnish (FIN) AF: 0.126 AC: 1333 AN: 10598

Middle Eastern (MID) AF: 0.180 AC: 53 AN: 294

European-Non Finnish (NFE) AF: 0.167 AC: 11354 AN: 68008

Other (OTH) AF: 0.137 AC: 289 AN: 2114

Alfa AF: 0.154 Hom.: 1513

Bravo AF: 0.110

TwinsUK AF: 0.182 AC: 675

ALSPAC AF: 0.164 AC: 633

ESP6500AA AF: 0.0270 AC: 101

ESP6500EA AF: 0.168 AC: 1378

ExAC AF: 0.125 AC: 15090

Asia WGS AF: 0.0520 AC: 183 AN: 3478

EpiCase AF: 0.174

EpiControl AF: 0.175

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not specified (3)
-	-	2	not provided (2)
-	-	2	Primary ciliary dyskinesia (2)
-	-	1	Primary ciliary dyskinesia 7 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.098
BayesDel_addAF	Benign	-0.52	T
BayesDel_noAF	Benign	-0.37
CADD	Benign	21
DANN	Benign	0.66
DEOGEN2	Benign	0.14	T
Eigen	Benign	0.089
Eigen_PC	Benign	0.061
FATHMM_MKL	Benign	0.72	D
LIST_S2	Benign	0.69	T
MetaRNN	Benign	0.0018	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.9	L
PhyloP100		1.8
PrimateAI	Benign	0.32	T
PROVEAN	Uncertain	-2.4	N
REVEL	Benign	0.26
Sift	Benign	0.14	T
Polyphen		0.96	D
Vest4		0.15
ClinPred		0.022	T
GERP RS		3.7
Varity_R		0.16
gMVP		0.12
Mutation Taster		=94/6	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs62441683; hg19: chr7-21628242;