chr5-13809020-G-A

Variant names:

• chr5-13809020-G-A
• rs112778044
• NM_001369.3:c.7752+24C>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.7752+24C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00422 in 1,612,822 control chromosomes in the GnomAD database, including 207 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.021 (98 hom., cov: 32)
  • Exomes 𝑓: 0.0025 (109 hom.)
• Consequence: DNAH5 NM_001369.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.226
• Publications: 1 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

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 5-13809020-G-A is Benign according to our data. Variant chr5-13809020-G-A is described in ClinVar as Benign. ClinVar VariationId is 258059.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0673 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAH5	NM_001369.3	MANE Select	c.7752+24C>T		intron	N/A	NP_001360.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAH5	ENST00000265104.5	TSL:1 MANE Select	c.7752+24C>T		intron	N/A	ENSP00000265104.4
	DNAH5	ENST00000681290.1		c.7707+24C>T		intron	N/A	ENSP00000505288.1
	DNAH5	ENST00000512443.1	TSL:3	n.608+24C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0208 AC: 3160 AN: 152090 Hom.: 96 Cov.: 32

Gnomad AFR AF: 0.0694

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0130

Gnomad ASJ AF: 0.00259

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.0000943

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.000573

Gnomad OTH AF: 0.0167

GnomAD2 exomes AF: 0.00620 AC: 1559 AN: 251428 AF XY: 0.00482

Gnomad AFR exome AF: 0.0748

Gnomad AMR exome AF: 0.00628

Gnomad ASJ exome AF: 0.00198

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000668

Gnomad OTH exome AF: 0.00391

GnomAD4 exome AF: 0.00250 AC: 3646 AN: 1460614 Hom.: 109 Cov.: 31 AF XY: 0.00218 AC XY: 1583 AN XY: 726714

African (AFR) AF: 0.0717 AC: 2395 AN: 33420

American (AMR) AF: 0.00682 AC: 305 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.00191 AC: 50 AN: 26120

East Asian (EAS) AF: 0.00 AC: 0 AN: 39676

South Asian (SAS) AF: 0.000232 AC: 20 AN: 86236

European-Finnish (FIN) AF: 0.0000749 AC: 4 AN: 53386

Middle Eastern (MID) AF: 0.0115 AC: 66 AN: 5762

European-Non Finnish (NFE) AF: 0.000409 AC: 454 AN: 1110946

Other (OTH) AF: 0.00583 AC: 352 AN: 60352

GnomAD4 genome AF: 0.0208 AC: 3167 AN: 152208 Hom.: 98 Cov.: 32 AF XY: 0.0200 AC XY: 1489 AN XY: 74426

African (AFR) AF: 0.0694 AC: 2879 AN: 41492

American (AMR) AF: 0.0130 AC: 199 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.00259 AC: 9 AN: 3472

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5180

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4822

European-Finnish (FIN) AF: 0.0000943 AC: 1 AN: 10600

Middle Eastern (MID) AF: 0.0102 AC: 3 AN: 294

European-Non Finnish (NFE) AF: 0.000573 AC: 39 AN: 68028

Other (OTH) AF: 0.0166 AC: 35 AN: 2114

Alfa AF: 0.0132 Hom.: 9

Bravo AF: 0.0244

Asia WGS AF: 0.00491 AC: 17 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)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	1.3
DANN	Benign	0.50
PhyloP100		-0.23
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: rs112778044; hg19: chr5-13809129;