rs141368864

chr5-13720950-T-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_001369.3(DNAH5):c.12279+50A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00584 in 1,613,016 control chromosomes in the GnomAD database, including 44 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0043 (3 hom., cov: 33)
  • Exomes 𝑓: 0.0060 (41 hom.)
• Consequence: DNAH5 NM_001369.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.177

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=-0.87).
• BP6: Variant 5-13720950-T-C is Benign according to our data. Variant chr5-13720950-T-C is described in ClinVar as [Benign]. Clinvar id is 257992.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00435 (662/152346) while in subpopulation NFE AF= 0.00704 (479/68028). AF 95% confidence interval is 0.00652. There are 3 homozygotes in gnomad4. There are 271 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DNAH5	NM_001369.3	c.12279+50A>G		intron_variant		ENST00000265104.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DNAH5	ENST00000265104.5	c.12279+50A>G		intron_variant		1	NM_001369.3	P4
DNAH5	ENST00000681290.1	c.12234+50A>G		intron_variant				A1

Frequencies

GnomAD3 genomes AF: 0.00436 AC: 663 AN: 152228 Hom.: 3 Cov.: 33

Gnomad AFR AF: 0.00152

Gnomad AMI AF: 0.00329

Gnomad AMR AF: 0.00478

Gnomad ASJ AF: 0.00691

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.000753

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00704

Gnomad OTH AF: 0.00526

GnomAD3 exomes AF: 0.00496 AC: 1236 AN: 249386 Hom.: 4 AF XY: 0.00505 AC XY: 683 AN XY: 135122

Gnomad AFR exome AF: 0.000945

Gnomad AMR exome AF: 0.00683

Gnomad ASJ exome AF: 0.00925

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000261

Gnomad FIN exome AF: 0.00111

Gnomad NFE exome AF: 0.00715

Gnomad OTH exome AF: 0.00938

GnomAD4 exome AF: 0.00599 AC: 8755 AN: 1460670 Hom.: 41 Cov.: 31 AF XY: 0.00587 AC XY: 4264 AN XY: 726696

Gnomad4 AFR exome AF: 0.000837

Gnomad4 AMR exome AF: 0.00700

Gnomad4 ASJ exome AF: 0.00877

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000232

Gnomad4 FIN exome AF: 0.00118

Gnomad4 NFE exome AF: 0.00692

Gnomad4 OTH exome AF: 0.00638

GnomAD4 genome AF: 0.00435 AC: 662 AN: 152346 Hom.: 3 Cov.: 33 AF XY: 0.00364 AC XY: 271 AN XY: 74500

Gnomad4 AFR AF: 0.00151

Gnomad4 AMR AF: 0.00471

Gnomad4 ASJ AF: 0.00691

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000414

Gnomad4 FIN AF: 0.000753

Gnomad4 NFE AF: 0.00704

Gnomad4 OTH AF: 0.00520

Alfa AF: 0.00593 Hom.: 2

Bravo AF: 0.00546

Asia WGS AF: 0.000577 AC: 2 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
Cadd	Benign	0.89
Dann	Benign	0.44

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: rs141368864; hg19: chr5-13721059;