rs13156044

Variant names:

• chr5-13867742-G-A
• rs13156044
• NM_001369.3:c.4053+32C>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.4053+32C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.12 in 1,559,750 control chromosomes in the GnomAD database, including 11,943 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.12 (1162 hom., cov: 32)
  • Exomes 𝑓: 0.12 (10781 hom.)
• Consequence: DNAH5 NM_001369.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -0.890
• Publications: 10 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

DNAH5-AS1 (HGNC:40187):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 5-13867742-G-A is Benign according to our data. Variant chr5-13867742-G-A is described in ClinVar as Benign. ClinVar VariationId is 258027.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.129 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.4053+32C>T		intron	N/A	NP_001360.1
	DNAH5-AS1	NR_199035.1		n.117+7187G>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.4053+32C>T		intron	N/A	ENSP00000265104.4
	DNAH5	ENST00000681290.1		c.4008+32C>T		intron	N/A	ENSP00000505288.1
	DNAH5-AS1	ENST00000503244.2	TSL:4	n.253+7187G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.121 AC: 18369 AN: 151944 Hom.: 1160 Cov.: 32

Gnomad AFR AF: 0.125

Gnomad AMI AF: 0.0559

Gnomad AMR AF: 0.0755

Gnomad ASJ AF: 0.0703

Gnomad EAS AF: 0.103

Gnomad SAS AF: 0.0469

Gnomad FIN AF: 0.174

Gnomad MID AF: 0.0791

Gnomad NFE AF: 0.131

Gnomad OTH AF: 0.109

GnomAD2 exomes AF: 0.107 AC: 26599 AN: 249558 AF XY: 0.105

Gnomad AFR exome AF: 0.120

Gnomad AMR exome AF: 0.0495

Gnomad ASJ exome AF: 0.0737

Gnomad EAS exome AF: 0.0990

Gnomad FIN exome AF: 0.167

Gnomad NFE exome AF: 0.130

Gnomad OTH exome AF: 0.111

GnomAD4 exome AF: 0.120 AC: 169031 AN: 1407686 Hom.: 10781 Cov.: 25 AF XY: 0.118 AC XY: 82873 AN XY: 703590

African (AFR) AF: 0.126 AC: 4081 AN: 32292

American (AMR) AF: 0.0543 AC: 2424 AN: 44638

Ashkenazi Jewish (ASJ) AF: 0.0732 AC: 1889 AN: 25800

East Asian (EAS) AF: 0.0915 AC: 3607 AN: 39422

South Asian (SAS) AF: 0.0496 AC: 4218 AN: 85118

European-Finnish (FIN) AF: 0.168 AC: 8962 AN: 53356

Middle Eastern (MID) AF: 0.0822 AC: 414 AN: 5038

European-Non Finnish (NFE) AF: 0.128 AC: 136543 AN: 1063374

Other (OTH) AF: 0.118 AC: 6893 AN: 58648

GnomAD4 genome AF: 0.121 AC: 18381 AN: 152064 Hom.: 1162 Cov.: 32 AF XY: 0.119 AC XY: 8819 AN XY: 74308

African (AFR) AF: 0.125 AC: 5170 AN: 41504

American (AMR) AF: 0.0754 AC: 1152 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.0703 AC: 244 AN: 3470

East Asian (EAS) AF: 0.104 AC: 538 AN: 5178

South Asian (SAS) AF: 0.0474 AC: 228 AN: 4814

European-Finnish (FIN) AF: 0.174 AC: 1829 AN: 10532

Middle Eastern (MID) AF: 0.0850 AC: 25 AN: 294

European-Non Finnish (NFE) AF: 0.131 AC: 8917 AN: 67986

Other (OTH) AF: 0.108 AC: 227 AN: 2102

Alfa AF: 0.122 Hom.: 3406

Bravo AF: 0.113

Asia WGS AF: 0.0880 AC: 306 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.053
DANN	Benign	0.71
PhyloP100		-0.89
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: rs13156044; hg19: chr5-13867851; COSMIC: COSV54243568;