5-13886165-T-G

Variant names:

• chr5-13886165-T-G
• rs199959119
• NM_001369.3:c.2578-36A>C

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001369.3(DNAH5):​c.2578-36A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. 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 0.000021 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: DNAH5 NM_001369.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.05
• Publications: 0 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: PanelApp Australia, Labcorp Genetics (formerly Invitae), G2P, ClinGen
• primary ciliary dyskinesia

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ENSG00000251423 (HGNC:40187):

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNAH5	NM_001369.3	c.2578-36A>C		intron_variant	Intron 17 of 78	ENST00000265104.5	NP_001360.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DNAH5	ENST00000265104.5	c.2578-36A>C		intron_variant	Intron 17 of 78	1	NM_001369.3	ENSP00000265104.4
DNAH5	ENST00000681290.1	c.2533-36A>C		intron_variant	Intron 17 of 78			ENSP00000505288.1
ENSG00000251423	ENST00000503244.2	n.254-10424T>G		intron_variant	Intron 1 of 2	4
ENSG00000251423	ENST00000637153.1	n.214-10424T>G		intron_variant	Intron 1 of 2	5

Frequencies

GnomAD3 genomes AF: 0.0000206 AC: 3 AN: 145530 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000449

Gnomad OTH AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1384786 Hom.: 0 Cov.: 29 AF XY: 0.00 AC XY: 0 AN XY: 687880

African (AFR) AF: 0.00 AC: 0 AN: 31296

American (AMR) AF: 0.00 AC: 0 AN: 38216

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25212

East Asian (EAS) AF: 0.00 AC: 0 AN: 37648

South Asian (SAS) AF: 0.00 AC: 0 AN: 81128

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 39668

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5160

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1068788

Other (OTH) AF: 0.00 AC: 0 AN: 57670

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000206 AC: 3 AN: 145546 Hom.: 0 Cov.: 32 AF XY: 0.0000284 AC XY: 2 AN XY: 70474

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 39672

American (AMR) AF: 0.00 AC: 0 AN: 14646

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3438

East Asian (EAS) AF: 0.00 AC: 0 AN: 4972

South Asian (SAS) AF: 0.00 AC: 0 AN: 4646

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 8206

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 278

European-Non Finnish (NFE) AF: 0.0000449 AC: 3 AN: 66754

Other (OTH) AF: 0.00 AC: 0 AN: 2030

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	1.9
DANN	Benign	0.67
PhyloP100		1.1

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.13		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs199959119; hg19: chr5-13886274;