chr5-13900435-T-G

Position:

• chr5-13900435-T-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The ENST00000265104.5(DNAH5):​c.2053-23A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00706 in 1,592,814 control chromosomes in the GnomAD database, including 119 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). There are indicators that this mutation may affect the branch point..

• Frequency:
  • Genomes: 𝑓 0.0051 (2 hom., cov: 32)
  • Exomes 𝑓: 0.0073 (117 hom.)
• Consequence: DNAH5 ENST00000265104.5 intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -0.00300

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]

ENSG00000251423 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: This place is a probable branch point but likely benign (scored 2 / 10). Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 5-13900435-T-G is Benign according to our data. Variant chr5-13900435-T-G is described in ClinVar as [Likely_benign]. Clinvar id is 258008.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.00509 (775/152320) while in subpopulation SAS AF= 0.03 (145/4828). AF 95% confidence interval is 0.0261. There are 2 homozygotes in gnomad4. There are 418 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DNAH5	NM_001369.3	c.2053-23A>C		intron_variant		ENST00000265104.5	NP_001360.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DNAH5	ENST00000265104.5	c.2053-23A>C		intron_variant		1	NM_001369.3	ENSP00000265104.4
DNAH5	ENST00000681290.1	c.2008-23A>C		intron_variant				ENSP00000505288.1
ENSG00000251423	ENST00000503244.2	n.3311T>G		non_coding_transcript_exon_variant	3/3	4
ENSG00000251423	ENST00000637153.1	n.3271T>G		non_coding_transcript_exon_variant	3/3	5

Frequencies

GnomAD3 genomes AF: 0.00512 AC: 780 AN: 152202 Hom.: 2 Cov.: 32

Gnomad AFR AF: 0.000941

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00759

Gnomad ASJ AF: 0.0138

Gnomad EAS AF: 0.00231

Gnomad SAS AF: 0.0306

Gnomad FIN AF: 0.00122

Gnomad MID AF: 0.0316

Gnomad NFE AF: 0.00560

Gnomad OTH AF: 0.00621

GnomAD3 exomes AF: 0.00958 AC: 2382 AN: 248738 Hom.: 39 AF XY: 0.0111 AC XY: 1499 AN XY: 134720

Gnomad AFR exome AF: 0.000567

Gnomad AMR exome AF: 0.00528

Gnomad ASJ exome AF: 0.0142

Gnomad EAS exome AF: 0.00220

Gnomad SAS exome AF: 0.0368

Gnomad FIN exome AF: 0.00301

Gnomad NFE exome AF: 0.00658

Gnomad OTH exome AF: 0.0139

GnomAD4 exome AF: 0.00727 AC: 10478 AN: 1440494 Hom.: 117 Cov.: 25 AF XY: 0.00843 AC XY: 6051 AN XY: 718114

Gnomad4 AFR exome AF: 0.00212

Gnomad4 AMR exome AF: 0.00546

Gnomad4 ASJ exome AF: 0.0139

Gnomad4 EAS exome AF: 0.00116

Gnomad4 SAS exome AF: 0.0375

Gnomad4 FIN exome AF: 0.00300

Gnomad4 NFE exome AF: 0.00512

Gnomad4 OTH exome AF: 0.00929

GnomAD4 genome AF: 0.00509 AC: 775 AN: 152320 Hom.: 2 Cov.: 32 AF XY: 0.00561 AC XY: 418 AN XY: 74492

Gnomad4 AFR AF: 0.000938

Gnomad4 AMR AF: 0.00758

Gnomad4 ASJ AF: 0.0138

Gnomad4 EAS AF: 0.00231

Gnomad4 SAS AF: 0.0300

Gnomad4 FIN AF: 0.00122

Gnomad4 NFE AF: 0.00560

Gnomad4 OTH AF: 0.00568

Alfa AF: 0.00767 Hom.: 1

Bravo AF: 0.00465

Asia WGS AF: 0.0170 AC: 58 AN: 3476

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Feb 18, 2020	- -

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

-

- -

Primary ciliary dyskinesia 3 Benign:1

Benign, criteria provided, single submitter

clinical testing

Pars Genome Lab

Jun 15, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.64
DANN	Benign	0.46
La Branchor		0.54
BranchPoint Hunter		2.0

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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: rs114717951; hg19: chr5-13900544;