5-13914687-T-C

Variant names:

• chr5-13914687-T-C
• rs13162553
• NM_001369.3:c.1198-45A>G

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.1198-45A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.391 in 1,580,620 control chromosomes in the GnomAD database, including 128,228 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.44 (15251 hom., cov: 32)
  • Exomes 𝑓: 0.39 (112977 hom.)
• Consequence: DNAH5 NM_001369.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -1.22
• Publications: 8 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 5-13914687-T-C is Benign according to our data. Variant chr5-13914687-T-C is described in ClinVar as Benign. ClinVar VariationId is 257988.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.83 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.1198-45A>G		intron	N/A	NP_001360.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAH5	ENST00000265104.5	TSL:1 MANE Select	c.1198-45A>G		intron	N/A	ENSP00000265104.4
	DNAH5	ENST00000682376.1		n.4821A>G		non_coding_transcript_exon	Exon 8 of 8
	DNAH5	ENST00000683967.1		n.2957A>G		non_coding_transcript_exon	Exon 9 of 10

Frequencies

GnomAD3 genomes AF: 0.436 AC: 66257 AN: 151800 Hom.: 15247 Cov.: 32

Gnomad AFR AF: 0.528

Gnomad AMI AF: 0.316

Gnomad AMR AF: 0.412

Gnomad ASJ AF: 0.409

Gnomad EAS AF: 0.852

Gnomad SAS AF: 0.372

Gnomad FIN AF: 0.327

Gnomad MID AF: 0.449

Gnomad NFE AF: 0.379

Gnomad OTH AF: 0.428

GnomAD2 exomes AF: 0.420 AC: 104640 AN: 248932 AF XY: 0.414

Gnomad AFR exome AF: 0.534

Gnomad AMR exome AF: 0.391

Gnomad ASJ exome AF: 0.422

Gnomad EAS exome AF: 0.861

Gnomad FIN exome AF: 0.329

Gnomad NFE exome AF: 0.376

Gnomad OTH exome AF: 0.410

GnomAD4 exome AF: 0.386 AC: 551574 AN: 1428702 Hom.: 112977 Cov.: 29 AF XY: 0.385 AC XY: 274039 AN XY: 712222

African (AFR) AF: 0.530 AC: 17210 AN: 32500

American (AMR) AF: 0.395 AC: 17591 AN: 44552

Ashkenazi Jewish (ASJ) AF: 0.420 AC: 10854 AN: 25830

East Asian (EAS) AF: 0.841 AC: 33078 AN: 39354

South Asian (SAS) AF: 0.356 AC: 30398 AN: 85492

European-Finnish (FIN) AF: 0.339 AC: 17858 AN: 52734

Middle Eastern (MID) AF: 0.422 AC: 2216 AN: 5248

European-Non Finnish (NFE) AF: 0.368 AC: 398292 AN: 1083744

Other (OTH) AF: 0.406 AC: 24077 AN: 59248

GnomAD4 genome AF: 0.436 AC: 66288 AN: 151918 Hom.: 15251 Cov.: 32 AF XY: 0.435 AC XY: 32280 AN XY: 74264

African (AFR) AF: 0.528 AC: 21873 AN: 41464

American (AMR) AF: 0.412 AC: 6292 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.409 AC: 1419 AN: 3466

East Asian (EAS) AF: 0.851 AC: 4400 AN: 5168

South Asian (SAS) AF: 0.373 AC: 1796 AN: 4820

European-Finnish (FIN) AF: 0.327 AC: 3456 AN: 10576

Middle Eastern (MID) AF: 0.442 AC: 129 AN: 292

European-Non Finnish (NFE) AF: 0.379 AC: 25731 AN: 67838

Other (OTH) AF: 0.428 AC: 904 AN: 2114

Alfa AF: 0.390 Hom.: 2241

Bravo AF: 0.450

Asia WGS AF: 0.573 AC: 1988 AN: 3476

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	-0.82
CADD	Benign	4.1
DANN	Benign	0.71
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: rs13162553; hg19: chr5-13914796;