rs606231238

Variant names:

• chr19-48311552-C-A
• NM_001364171.2:c.597+1G>T

Your query was ambiguous. Multiple possible variants found:

• chr19-48311552-C-A
• chr19-48311552-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PVS1_Moderate PM2

The NM_001364171.2(ODAD1):​c.597+1G>T variant causes a splice donor, intron change. The variant allele was found at a frequency of 0.000000722 in 1,385,918 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. 3/3 splice prediction tools predicting alterations to normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 7.2e-7 (0 hom.)
• Consequence: ODAD1 NM_001364171.2 splice_donor, intron
• Scores: Splicing: ADA: 1.000
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.71

Genes affected

ODAD1 (HGNC:26560): (outer dynein arm docking complex subunit 1) This gene encodes a coiled-coil domain-containing protein that is a component of the outer dynein arm docking complex in cilia cells. Mutations in this gene may cause primary ciliary dyskinesia 20. [provided by RefSeq, May 2013]

ACMG classification

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PVS1: Splicing +-2 bp (donor or acceptor) variant, product NOT destroyed by NMD, known LOF gene, truncates exone, which is 0.053672317 fraction of the gene. No cryptic splice site detected. Exon removal is inframe change.
• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ODAD1	NM_001364171.2	c.597+1G>T		splice_donor_variant, intron_variant	Intron 7 of 15	ENST00000674294.1	NP_001351100.1
ODAD1	NM_144577.4	c.486+1G>T		splice_donor_variant, intron_variant	Intron 5 of 13		NP_653178.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ODAD1	ENST00000674294.1	c.597+1G>T		splice_donor_variant, intron_variant	Intron 7 of 15		NM_001364171.2	ENSP00000501363.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 7.22e-7 AC: 1 AN: 1385918 Hom.: 0 Cov.: 28 AF XY: 0.00000146 AC XY: 1 AN XY: 684510

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.37e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.58	D
BayesDel_noAF	Uncertain	0.060
CADD	Pathogenic	32
DANN	Uncertain	0.99
Eigen	Pathogenic	0.87
Eigen_PC	Uncertain	0.64
FATHMM_MKL	Uncertain	0.87	D
GERP RS		4.4

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Pathogenic	1.0
dbscSNV1_RF	Pathogenic	0.87
SpliceAI score (max)		1.0		Details are displayed if max score is > 0.2
DS_DG_spliceai		0.57		Position offset: -46
DS_DL_spliceai		1.0		Position offset: 1

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr19-48814809;