rs1502050

Positions:

• chr5-13779634-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001369.3(DNAH5):​c.8951+1195A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.313 in 152,060 control chromosomes in the GnomAD database, including 8,004 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 0.31 (8004 hom., cov: 32)
• Consequence: DNAH5 NM_001369.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.360

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.429 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DNAH5	NM_001369.3	c.8951+1195A>G		intron_variant		ENST00000265104.5	NP_001360.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DNAH5	ENST00000265104.5	c.8951+1195A>G		intron_variant		1	NM_001369.3	ENSP00000265104	P4
DNAH5	ENST00000681290.1	c.8906+1195A>G		intron_variant				ENSP00000505288	A1

Frequencies

GnomAD3 genomes AF: 0.313 AC: 47548 AN: 151942 Hom.: 7975 Cov.: 32

Gnomad AFR AF: 0.382

Gnomad AMI AF: 0.157

Gnomad AMR AF: 0.273

Gnomad ASJ AF: 0.205

Gnomad EAS AF: 0.112

Gnomad SAS AF: 0.442

Gnomad FIN AF: 0.441

Gnomad MID AF: 0.241

Gnomad NFE AF: 0.275

Gnomad OTH AF: 0.282

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

GnomAD4 genome AF: 0.313 AC: 47631 AN: 152060 Hom.: 8004 Cov.: 32 AF XY: 0.320 AC XY: 23754 AN XY: 74324

Gnomad4 AFR AF: 0.382

Gnomad4 AMR AF: 0.273

Gnomad4 ASJ AF: 0.205

Gnomad4 EAS AF: 0.112

Gnomad4 SAS AF: 0.444

Gnomad4 FIN AF: 0.441

Gnomad4 NFE AF: 0.275

Gnomad4 OTH AF: 0.287

Alfa AF: 0.267 Hom.: 6937

Bravo AF: 0.297

Asia WGS AF: 0.333 AC: 1156 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	3.8
DANN	Benign	0.59

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: rs1502050; hg19: chr5-13779743;