rs13162553

Variant names:

• chr5-13914687-T-A
• rs13162553
• NM_001369.3:c.1198-45A>T

Your query was ambiguous. Multiple possible variants found:

• chr5-13914687-T-A
• chr5-13914687-T-C
• chr5-13914687-T-G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001369.3(DNAH5):​c.1198-45A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000138 in 1,444,894 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: DNAH5 NM_001369.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.22
• Publications: 8 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 -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).

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.1198-45A>T		intron	N/A	NP_001360.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAH5	ENST00000265104.5	TSL:1 MANE Select	c.1198-45A>T		intron	N/A	ENSP00000265104.4
	DNAH5	ENST00000682376.1		n.4821A>T		non_coding_transcript_exon	Exon 8 of 8
	DNAH5	ENST00000683967.1		n.2957A>T		non_coding_transcript_exon	Exon 9 of 10

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000138 AC: 2 AN: 1444894 Hom.: 0 Cov.: 29 AF XY: 0.00000139 AC XY: 1 AN XY: 719666

African (AFR) AF: 0.00 AC: 0 AN: 32890

American (AMR) AF: 0.00 AC: 0 AN: 44610

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25960

East Asian (EAS) AF: 0.00 AC: 0 AN: 39404

South Asian (SAS) AF: 0.00 AC: 0 AN: 85806

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52820

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5298

European-Non Finnish (NFE) AF: 0.00000182 AC: 2 AN: 1098340

Other (OTH) AF: 0.00 AC: 0 AN: 59766

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 2241

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	3.2
DANN	Benign	0.68
PhyloP100		-1.2

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

Other links and lift over

dbSNP: rs13162553; hg19: chr5-13914796;