rs77448980

Variant names:

• chr7-21901205-A-G
• rs77448980
• NM_001277115.2:c.13502A>G

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.13502A>G​(p.Lys4501Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.076 in 1,613,064 control chromosomes in the GnomAD database, including 5,191 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.062 (328 hom., cov: 33)
  • Exomes 𝑓: 0.077 (4863 hom.)
• Consequence: DNAH11 NM_001277115.2 missense
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:7
• Conservation: PhyloP100: 0.797
• Publications: 9 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]

CDCA7L (HGNC:30777): (cell division cycle associated 7 like) Acts upstream of or within positive regulation of cell population proliferation. Located in cytosol; fibrillar center; and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0018184781).
• BP6: Variant 7-21901205-A-G is Benign according to our data. Variant chr7-21901205-A-G is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 163130.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.101 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.13502A>G	p.Lys4501Arg	missense	Exon 82 of 82	NP_001264044.1	Q96DT5
	CDCA7L	NM_018719.5	MANE Select	c.*1117T>C		3_prime_UTR	Exon 10 of 10	NP_061189.2
	CDCA7L	NM_001127370.3		c.*1117T>C		3_prime_UTR	Exon 11 of 11	NP_001120842.1	Q96GN5-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAH11	ENST00000409508.8	TSL:5 MANE Select	c.13502A>G	p.Lys4501Arg	missense	Exon 82 of 82	ENSP00000475939.1	Q96DT5
	CDCA7L	ENST00000406877.8	TSL:1 MANE Select	c.*1117T>C		3_prime_UTR	Exon 10 of 10	ENSP00000383986.3	Q96GN5-1
	CDCA7L	ENST00000934293.1		c.*1117T>C		3_prime_UTR	Exon 10 of 10	ENSP00000604352.1

Frequencies

GnomAD3 genomes AF: 0.0619 AC: 9401 AN: 151988 Hom.: 325 Cov.: 33

Gnomad AFR AF: 0.0385

Gnomad AMI AF: 0.185

Gnomad AMR AF: 0.0389

Gnomad ASJ AF: 0.0525

Gnomad EAS AF: 0.0273

Gnomad SAS AF: 0.108

Gnomad FIN AF: 0.0592

Gnomad MID AF: 0.0665

Gnomad NFE AF: 0.0800

Gnomad OTH AF: 0.0582

GnomAD2 exomes AF: 0.0668 AC: 16502 AN: 246936 AF XY: 0.0707

Gnomad AFR exome AF: 0.0388

Gnomad AMR exome AF: 0.0269

Gnomad ASJ exome AF: 0.0572

Gnomad EAS exome AF: 0.0300

Gnomad FIN exome AF: 0.0602

Gnomad NFE exome AF: 0.0802

Gnomad OTH exome AF: 0.0637

GnomAD4 exome AF: 0.0775 AC: 113166 AN: 1460958 Hom.: 4863 Cov.: 34 AF XY: 0.0784 AC XY: 56943 AN XY: 726744

African (AFR) AF: 0.0393 AC: 1316 AN: 33470

American (AMR) AF: 0.0280 AC: 1253 AN: 44680

Ashkenazi Jewish (ASJ) AF: 0.0550 AC: 1436 AN: 26124

East Asian (EAS) AF: 0.0159 AC: 631 AN: 39700

South Asian (SAS) AF: 0.106 AC: 9164 AN: 86214

European-Finnish (FIN) AF: 0.0630 AC: 3362 AN: 53402

Middle Eastern (MID) AF: 0.0676 AC: 390 AN: 5768

European-Non Finnish (NFE) AF: 0.0821 AC: 91211 AN: 1111272

Other (OTH) AF: 0.0730 AC: 4403 AN: 60328

GnomAD4 genome AF: 0.0619 AC: 9416 AN: 152106 Hom.: 328 Cov.: 33 AF XY: 0.0604 AC XY: 4495 AN XY: 74362

African (AFR) AF: 0.0387 AC: 1608 AN: 41532

American (AMR) AF: 0.0387 AC: 591 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.0525 AC: 182 AN: 3466

East Asian (EAS) AF: 0.0274 AC: 142 AN: 5180

South Asian (SAS) AF: 0.108 AC: 522 AN: 4812

European-Finnish (FIN) AF: 0.0592 AC: 628 AN: 10610

Middle Eastern (MID) AF: 0.0612 AC: 18 AN: 294

European-Non Finnish (NFE) AF: 0.0799 AC: 5431 AN: 67940

Other (OTH) AF: 0.0595 AC: 125 AN: 2102

Alfa AF: 0.0717 Hom.: 869

Bravo AF: 0.0582

TwinsUK AF: 0.0831 AC: 308

ALSPAC AF: 0.0755 AC: 291

ESP6500AA AF: 0.0423 AC: 163

ESP6500EA AF: 0.0822 AC: 682

ExAC AF: 0.0703 AC: 8504

Asia WGS AF: 0.0870 AC: 300 AN: 3478

EpiCase AF: 0.0787

EpiControl AF: 0.0756

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)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.080
BayesDel_addAF	Benign	-0.71	T
BayesDel_noAF	Benign	-0.71
CADD	Benign	7.5
DANN	Benign	0.81
DEOGEN2	Benign	0.059	T
Eigen	Benign	-0.79
Eigen_PC	Benign	-0.72
FATHMM_MKL	Benign	0.27	N
LIST_S2	Benign	0.67	T
MetaRNN	Benign	0.0018	T
MetaSVM	Benign	-0.95	T
PhyloP100		0.80
PrimateAI	Benign	0.33	T
PROVEAN	Benign	-1.6	N
REVEL	Benign	0.043
Sift	Benign	0.37	T
Vest4		0.038
ClinPred		0.0029	T
GERP RS		3.6
Varity_R		0.032
gMVP		0.17
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: rs77448980; hg19: chr7-21940823; COSMIC: COSV60943279; COSMIC: COSV60943279;