ENST00000681290.1:c.12+24654T>C

Variant names:

• chr5-13986994-A-G
• rs1031006
• ENST00000681290.1:c.12+24654T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000681290.1(DNAH5):​c.12+24654T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.39 in 151,960 control chromosomes in the GnomAD database, including 11,877 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.39 (11877 hom., cov: 31)
• Consequence: DNAH5 ENST00000681290.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.78
• Publications: 5 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: G2P, ClinGen, Labcorp Genetics (formerly Invitae)
• primary ciliary dyskinesia

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ENSG00000307550 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.07).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.662 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000681290.1. 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
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAH5	ENST00000681290.1		c.12+24654T>C		intron	N/A	ENSP00000505288.1	A0A7P0Z455
	ENSG00000307550	ENST00000827039.1		n.338A>G		non_coding_transcript_exon	Exon 2 of 2

Frequencies

GnomAD3 genomes AF: 0.390 AC: 59200 AN: 151842 Hom.: 11862 Cov.: 31

Gnomad AFR AF: 0.437

Gnomad AMI AF: 0.364

Gnomad AMR AF: 0.382

Gnomad ASJ AF: 0.337

Gnomad EAS AF: 0.681

Gnomad SAS AF: 0.324

Gnomad FIN AF: 0.346

Gnomad MID AF: 0.402

Gnomad NFE AF: 0.356

Gnomad OTH AF: 0.377

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

GnomAD4 genome AF: 0.390 AC: 59262 AN: 151960 Hom.: 11877 Cov.: 31 AF XY: 0.390 AC XY: 28963 AN XY: 74274

African (AFR) AF: 0.437 AC: 18111 AN: 41418

American (AMR) AF: 0.382 AC: 5839 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.337 AC: 1168 AN: 3470

East Asian (EAS) AF: 0.681 AC: 3505 AN: 5146

South Asian (SAS) AF: 0.322 AC: 1553 AN: 4816

European-Finnish (FIN) AF: 0.346 AC: 3655 AN: 10550

Middle Eastern (MID) AF: 0.405 AC: 119 AN: 294

European-Non Finnish (NFE) AF: 0.356 AC: 24184 AN: 67976

Other (OTH) AF: 0.379 AC: 797 AN: 2104

Alfa AF: 0.357 Hom.: 17109

Bravo AF: 0.395

Asia WGS AF: 0.509 AC: 1770 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.1
CADD	Benign	0.19
DANN	Benign	0.22
PhyloP100		-1.8

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs1031006; hg19: chr5-13987103;