5-13769865-C-T

Position:

• chr5-13769865-C-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.9606-250G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.312 in 152,086 control chromosomes in the GnomAD database, including 7,936 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.31 (7936 hom., cov: 33)
• Consequence: DNAH5 NM_001369.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.514

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 5-13769865-C-T is Benign according to our data. Variant chr5-13769865-C-T is described in ClinVar as [Benign]. Clinvar id is 1271906.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.425 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DNAH5	NM_001369.3	c.9606-250G>A		intron_variant		ENST00000265104.5	NP_001360.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DNAH5	ENST00000265104.5	c.9606-250G>A		intron_variant		1	NM_001369.3	ENSP00000265104	P4
DNAH5	ENST00000681290.1	c.9561-250G>A		intron_variant				ENSP00000505288	A1
DNAH5	ENST00000504001.3	n.318-250G>A		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.312 AC: 47375 AN: 151966 Hom.: 7914 Cov.: 33

Gnomad AFR AF: 0.380

Gnomad AMI AF: 0.157

Gnomad AMR AF: 0.271

Gnomad ASJ AF: 0.205

Gnomad EAS AF: 0.113

Gnomad SAS AF: 0.438

Gnomad FIN AF: 0.443

Gnomad MID AF: 0.241

Gnomad NFE AF: 0.274

Gnomad OTH AF: 0.280

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.312 AC: 47448 AN: 152086 Hom.: 7936 Cov.: 33 AF XY: 0.319 AC XY: 23698 AN XY: 74328

Gnomad4 AFR AF: 0.380

Gnomad4 AMR AF: 0.271

Gnomad4 ASJ AF: 0.205

Gnomad4 EAS AF: 0.113

Gnomad4 SAS AF: 0.440

Gnomad4 FIN AF: 0.443

Gnomad4 NFE AF: 0.274

Gnomad4 OTH AF: 0.284

Alfa AF: 0.262 Hom.: 8628

Bravo AF: 0.295

Asia WGS AF: 0.328 AC: 1138 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

Nov 10, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	2.9
DANN	Benign	0.69

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs7715811; hg19: chr5-13769974;