NM_001369.3:c.5281C>A

Variant names:

• chr5-13841895-G-T
• rs148891849
• NM_001369.3:c.5281C>A

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Moderate BP6_Moderate

The NM_001369.3(DNAH5):​c.5281C>A​(p.Arg1761Arg) variant causes a synonymous change. The variant allele was found at a frequency of 0.0000102 in 984,824 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0 (0 hom., cov: 25)
  • Exomes 𝑓: 0.000010 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: DNAH5 NM_001369.3 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter U:1 B:1
• Conservation: PhyloP100: 3.99
• 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: PanelApp Australia, Labcorp Genetics (formerly Invitae), G2P, ClinGen
• primary ciliary dyskinesia

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.39).
• BP6: Variant 5-13841895-G-T is Benign according to our data. Variant chr5-13841895-G-T is described in ClinVar as Likely_benign. ClinVar VariationId is 702835.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001369.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAH5	NM_001369.3	MANE Select	c.5281C>A	p.Arg1761Arg	synonymous	Exon 33 of 79	NP_001360.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAH5	ENST00000265104.5	TSL:1 MANE Select	c.5281C>A	p.Arg1761Arg	synonymous	Exon 33 of 79	ENSP00000265104.4
	DNAH5	ENST00000681290.1		c.5236C>A	p.Arg1746Arg	synonymous	Exon 33 of 79	ENSP00000505288.1

Frequencies

GnomAD3 genomes AF: 0.00 AC: 0 AN: 108874 Hom.: 0 Cov.: 25

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: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00000433 AC: 1 AN: 231214 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000950

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000102 AC: 10 AN: 984824 Hom.: 0 Cov.: 26 AF XY: 0.0000139 AC XY: 7 AN XY: 502812

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

African (AFR) AF: 0.00 AC: 0 AN: 23556

American (AMR) AF: 0.00 AC: 0 AN: 40022

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19590

East Asian (EAS) AF: 0.00 AC: 0 AN: 28272

South Asian (SAS) AF: 0.00 AC: 0 AN: 74568

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 44286

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4064

European-Non Finnish (NFE) AF: 0.0000141 AC: 10 AN: 709458

Other (OTH) AF: 0.00 AC: 0 AN: 41008

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000512238), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 108920 Hom.: 0 Cov.: 25 AF XY: 0.00 AC XY: 0 AN XY: 49226

African (AFR) AF: 0.00 AC: 0 AN: 28092

American (AMR) AF: 0.00 AC: 0 AN: 7558

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3172

East Asian (EAS) AF: 0.00 AC: 0 AN: 3592

South Asian (SAS) AF: 0.00 AC: 0 AN: 3068

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 2786

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 98

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 58328

Other (OTH) AF: 0.00 AC: 0 AN: 1412

Alfa AF: 0.00 Hom.: 1

ClinVar

Significance: Likely benign

Submissions summary: Uncertain:1 Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Primary ciliary dyskinesia Uncertain:1 Benign:1

Nov 04, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Oct 26, 2020

Natera, Inc.

Significance: Uncertain significance

Review Status: no assertion criteria provided

Collection Method: clinical testing

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.39
CADD	Benign	12
DANN	Benign	0.55
PhyloP100		4.0

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.12		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: rs148891849; hg19: chr5-13842004;