5-13884851-A-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001369.3(DNAH5):c.2983+138T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.432 in 1,356,056 control chromosomes in the GnomAD database, including 128,976 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.44 (14776 hom., cov: 33)
  • Exomes 𝑓: 0.43 (114200 hom.)
• Consequence: DNAH5 NM_001369.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.160

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BP6: Variant 5-13884851-A-T is Benign according to our data. Variant chr5-13884851-A-T is described in ClinVar as [Benign]. Clinvar id is 1238691.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.707 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DNAH5	NM_001369.3	c.2983+138T>A		intron_variant		ENST00000265104.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DNAH5	ENST00000265104.5	c.2983+138T>A		intron_variant		1	NM_001369.3	P4
	ENST00000503244.2	n.254-11738A>T		intron_variant, non_coding_transcript_variant		4
DNAH5	ENST00000681290.1	c.2938+138T>A		intron_variant				A1
	ENST00000637153.1	n.214-11738A>T		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.438 AC: 66561 AN: 151978 Hom.: 14769 Cov.: 33

Gnomad AFR AF: 0.439

Gnomad AMI AF: 0.426

Gnomad AMR AF: 0.419

Gnomad ASJ AF: 0.422

Gnomad EAS AF: 0.726

Gnomad SAS AF: 0.366

Gnomad FIN AF: 0.441

Gnomad MID AF: 0.389

Gnomad NFE AF: 0.425

Gnomad OTH AF: 0.441

GnomAD4 exome AF: 0.431 AC: 519226 AN: 1203960 Hom.: 114200 AF XY: 0.429 AC XY: 257340 AN XY: 600132

Gnomad4 AFR exome AF: 0.435

Gnomad4 AMR exome AF: 0.408

Gnomad4 ASJ exome AF: 0.423

Gnomad4 EAS exome AF: 0.735

Gnomad4 SAS exome AF: 0.347

Gnomad4 FIN exome AF: 0.450

Gnomad4 NFE exome AF: 0.426

Gnomad4 OTH exome AF: 0.439

GnomAD4 genome AF: 0.438 AC: 66599 AN: 152096 Hom.: 14776 Cov.: 33 AF XY: 0.438 AC XY: 32579 AN XY: 74354

Gnomad4 AFR AF: 0.439

Gnomad4 AMR AF: 0.418

Gnomad4 ASJ AF: 0.422

Gnomad4 EAS AF: 0.726

Gnomad4 SAS AF: 0.365

Gnomad4 FIN AF: 0.441

Gnomad4 NFE AF: 0.425

Gnomad4 OTH AF: 0.440

Alfa AF: 0.413 Hom.: 1582

Bravo AF: 0.438

Asia WGS AF: 0.507 AC: 1761 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Aug 15, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
Cadd	Benign	0.80
Dann	Benign	0.26

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

Publications

LitVar

Other links and lift over

dbSNP: rs10866504; hg19: chr5-13884960;