5-13870727-G-A

Variant names:

• chr5-13870727-G-A
• rs35621834
• NM_001369.3:c.3834+40C>T

Variant summary

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

The NM_001369.3(DNAH5):​c.3834+40C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.123 in 1,546,678 control chromosomes in the GnomAD database, including 12,573 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.10 (965 hom., cov: 32)
  • Exomes 𝑓: 0.12 (11608 hom.)
• Consequence: DNAH5 NM_001369.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 1.17
• Publications: 5 publications found

Genes affected

DNAH5 (HGNC:2950): (dynein axonemal heavy chain 5) This gene encodes a dynein protein, which is part of a microtubule-associated motor protein complex consisting of heavy, light, and intermediate chains. This protein is an axonemal heavy chain dynein. It functions as a force-generating protein with ATPase activity, whereby the release of ADP is thought to produce the force-producing power stroke. Mutations in this gene cause primary ciliary dyskinesia type 3, as well as Kartagener syndrome, which are both diseases due to ciliary defects. [provided by RefSeq, Oct 2009]

DNAH5 Gene-Disease associations (from GenCC):

• primary ciliary dyskinesia 3

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: PanelApp Australia, Labcorp Genetics (formerly Invitae), G2P, ClinGen
• primary ciliary dyskinesia

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ENSG00000251423 (HGNC:40187):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BP6: Variant 5-13870727-G-A is Benign according to our data. Variant chr5-13870727-G-A is described in ClinVar as Benign. ClinVar VariationId is 258022.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.135 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001369.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAH5	NM_001369.3	MANE Select	c.3834+40C>T		intron	N/A	NP_001360.1
	DNAH5-AS1	NR_199035.1		n.117+10172G>A		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAH5	ENST00000265104.5	TSL:1 MANE Select	c.3834+40C>T		intron	N/A	ENSP00000265104.4
	DNAH5	ENST00000681290.1		c.3789+40C>T		intron	N/A	ENSP00000505288.1
	ENSG00000251423	ENST00000503244.2	TSL:4	n.253+10172G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.104 AC: 15809 AN: 151968 Hom.: 964 Cov.: 32

Gnomad AFR AF: 0.0572

Gnomad AMI AF: 0.0559

Gnomad AMR AF: 0.0669

Gnomad ASJ AF: 0.0677

Gnomad EAS AF: 0.103

Gnomad SAS AF: 0.0466

Gnomad FIN AF: 0.173

Gnomad MID AF: 0.0728

Gnomad NFE AF: 0.137

Gnomad OTH AF: 0.0986

GnomAD2 exomes AF: 0.103 AC: 24392 AN: 237060 AF XY: 0.103

Gnomad AFR exome AF: 0.0498

Gnomad AMR exome AF: 0.0461

Gnomad ASJ exome AF: 0.0723

Gnomad EAS exome AF: 0.0983

Gnomad FIN exome AF: 0.168

Gnomad NFE exome AF: 0.134

Gnomad OTH exome AF: 0.110

GnomAD4 exome AF: 0.125 AC: 173851 AN: 1394592 Hom.: 11608 Cov.: 23 AF XY: 0.122 AC XY: 85301 AN XY: 696856

African (AFR) AF: 0.0535 AC: 1721 AN: 32170

American (AMR) AF: 0.0502 AC: 2198 AN: 43762

Ashkenazi Jewish (ASJ) AF: 0.0722 AC: 1837 AN: 25444

East Asian (EAS) AF: 0.0915 AC: 3596 AN: 39282

South Asian (SAS) AF: 0.0495 AC: 4170 AN: 84174

European-Finnish (FIN) AF: 0.169 AC: 8842 AN: 52306

Middle Eastern (MID) AF: 0.0778 AC: 430 AN: 5530

European-Non Finnish (NFE) AF: 0.137 AC: 144313 AN: 1053904

Other (OTH) AF: 0.116 AC: 6744 AN: 58020

GnomAD4 genome AF: 0.104 AC: 15818 AN: 152086 Hom.: 965 Cov.: 32 AF XY: 0.102 AC XY: 7571 AN XY: 74340

African (AFR) AF: 0.0572 AC: 2375 AN: 41514

American (AMR) AF: 0.0669 AC: 1020 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.0677 AC: 235 AN: 3470

East Asian (EAS) AF: 0.104 AC: 539 AN: 5184

South Asian (SAS) AF: 0.0471 AC: 227 AN: 4820

European-Finnish (FIN) AF: 0.173 AC: 1824 AN: 10558

Middle Eastern (MID) AF: 0.0782 AC: 23 AN: 294

European-Non Finnish (NFE) AF: 0.137 AC: 9317 AN: 67966

Other (OTH) AF: 0.0980 AC: 207 AN: 2112

Alfa AF: 0.115 Hom.: 202

Bravo AF: 0.0936

Asia WGS AF: 0.0830 AC: 289 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

Nov 10, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

not specified Benign:1

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Primary ciliary dyskinesia 3 Benign:1

Jun 15, 2021

Pars Genome Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	9.8
DANN	Benign	0.72
PhyloP100		1.2
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: rs35621834; hg19: chr5-13870836; COSMIC: COSV54243518;