rs3922641

Variant names:

• chr7-775151-G-A
• rs3922641
• NM_017802.4:c.2228G>A

Your query was ambiguous. Multiple possible variants found:

• chr7-775151-G-A
• chr7-775151-G-C
• chr7-775151-G-T

Variant summary

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

The NM_017802.4(DNAAF5):​c.2228G>A​(p.Arg743Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.615 in 1,613,026 control chromosomes in the GnomAD database, including 306,208 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 Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.64 (31879 hom., cov: 32)
  • Exomes 𝑓: 0.61 (274329 hom.)
• Consequence: DNAAF5 NM_017802.4 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: 0.716
• Publications: 40 publications found

Genes affected

DNAAF5 (HGNC:26013): (dynein axonemal assembly factor 5) The protein encoded by this gene is essential for the preassembly or stability of axonemal dynein arms, and is found only in organisms with motile cilia and flagella. Mutations in this gene are associated with primary ciliary dyskinesia-18, a disorder characterized by abnormalities of motile cilia. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Feb 2013]

DNAAF5 Gene-Disease associations (from GenCC):

• primary ciliary dyskinesia 18

  Inheritance: AR Classification: STRONG, MODERATE Submitted by: G2P, Ambry Genetics, PanelApp Australia, Labcorp Genetics (formerly Invitae)
• 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=4.737047E-6).
• BP6: Variant 7-775151-G-A is Benign according to our data. Variant chr7-775151-G-A is described in ClinVar as Benign. ClinVar VariationId is 260932.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.698 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNAAF5	NM_017802.4	c.2228G>A	p.Arg743Lys	missense_variant	Exon 11 of 13	ENST00000297440.11	NP_060272.3
DNAAF5	XM_024446813.2	c.2228G>A	p.Arg743Lys	missense_variant	Exon 11 of 12		XP_024302581.1
DNAAF5	NR_075098.2	n.2188G>A		non_coding_transcript_exon_variant	Exon 11 of 13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DNAAF5	ENST00000297440.11	c.2228G>A	p.Arg743Lys	missense_variant	Exon 11 of 13	1	NM_017802.4	ENSP00000297440.6
DNAAF5	ENST00000403952.3	c.503G>A	p.Arg168Lys	missense_variant	Exon 4 of 6	1		ENSP00000384884.3
DNAAF5	ENST00000440747.5	c.1631G>A	p.Arg544Lys	missense_variant	Exon 11 of 13	2		ENSP00000403165.1

Frequencies

GnomAD3 genomes AF: 0.644 AC: 97883 AN: 151928 Hom.: 31830 Cov.: 32

Gnomad AFR AF: 0.705

Gnomad AMI AF: 0.559

Gnomad AMR AF: 0.673

Gnomad ASJ AF: 0.561

Gnomad EAS AF: 0.625

Gnomad SAS AF: 0.669

Gnomad FIN AF: 0.666

Gnomad MID AF: 0.560

Gnomad NFE AF: 0.603

Gnomad OTH AF: 0.650

GnomAD2 exomes AF: 0.623 AC: 156526 AN: 251100 AF XY: 0.622

Gnomad AFR exome AF: 0.703

Gnomad AMR exome AF: 0.619

Gnomad ASJ exome AF: 0.582

Gnomad EAS exome AF: 0.633

Gnomad FIN exome AF: 0.662

Gnomad NFE exome AF: 0.602

Gnomad OTH exome AF: 0.615

GnomAD4 exome AF: 0.612 AC: 894039 AN: 1460980 Hom.: 274329 Cov.: 44 AF XY: 0.612 AC XY: 444980 AN XY: 726822

African (AFR) AF: 0.716 AC: 23952 AN: 33450

American (AMR) AF: 0.627 AC: 28022 AN: 44706

Ashkenazi Jewish (ASJ) AF: 0.579 AC: 15128 AN: 26126

East Asian (EAS) AF: 0.605 AC: 24026 AN: 39694

South Asian (SAS) AF: 0.644 AC: 55581 AN: 86242

European-Finnish (FIN) AF: 0.662 AC: 35325 AN: 53370

Middle Eastern (MID) AF: 0.594 AC: 3425 AN: 5766

European-Non Finnish (NFE) AF: 0.604 AC: 671343 AN: 1111252

Other (OTH) AF: 0.617 AC: 37237 AN: 60374

GnomAD4 genome AF: 0.644 AC: 97980 AN: 152046 Hom.: 31879 Cov.: 32 AF XY: 0.647 AC XY: 48100 AN XY: 74320

African (AFR) AF: 0.705 AC: 29233 AN: 41458

American (AMR) AF: 0.673 AC: 10271 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.561 AC: 1949 AN: 3472

East Asian (EAS) AF: 0.625 AC: 3235 AN: 5180

South Asian (SAS) AF: 0.669 AC: 3224 AN: 4820

European-Finnish (FIN) AF: 0.666 AC: 7036 AN: 10564

Middle Eastern (MID) AF: 0.568 AC: 167 AN: 294

European-Non Finnish (NFE) AF: 0.603 AC: 40976 AN: 67966

Other (OTH) AF: 0.654 AC: 1380 AN: 2110

Alfa AF: 0.619 Hom.: 83514

Bravo AF: 0.647

TwinsUK AF: 0.593 AC: 2199

ALSPAC AF: 0.624 AC: 2406

ESP6500AA AF: 0.693 AC: 3053

ESP6500EA AF: 0.593 AC: 5101

ExAC AF: 0.621 AC: 75330

Asia WGS AF: 0.703 AC: 2444 AN: 3478

EpiCase AF: 0.609

EpiControl AF: 0.607

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:2

-

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Mar 29, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency -

Primary ciliary dyskinesia Benign:2

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jul 07, 2016

Ambry Genetics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Primary ciliary dyskinesia 18 Benign:1

Jul 14, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided Benign:1

Nov 12, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.065
BayesDel_addAF	Benign	-0.59	T
BayesDel_noAF	Benign	-0.48
CADD	Benign	12
DANN	Benign	0.86
DEOGEN2	Benign	0.030	T;T
Eigen	Benign	-1.1
Eigen_PC	Benign	-0.80
FATHMM_MKL	Benign	0.14	N
LIST_S2	Benign	0.14	T;T
MetaRNN	Benign	0.0000047	T;T
MetaSVM	Benign	-0.93	T
PhyloP100		0.72
PrimateAI	Benign	0.44	T
PROVEAN	Benign	1.6	N;N
REVEL	Benign	0.072
Sift	Benign	1.0	T;T
Sift4G	Benign	1.0	T;T
Polyphen		0.0	B;B
Vest4		0.032
MPC		0.16
ClinPred		0.00081	T
GERP RS		2.8
Varity_R		0.057
gMVP		0.085
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: rs3922641; hg19: chr7-814788; COSMIC: COSV108096225; COSMIC: COSV108096225;