NM_018076.5:c.937-7A>G

Variant names:

• chr10-27971320-T-C
• rs370699691
• NM_018076.5:c.937-7A>G

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Strong BP6_Moderate

The NM_018076.5(ODAD2):​c.937-7A>G variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000357 in 1,578,556 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 2/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00018 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00038 (0 hom.)
• Consequence: ODAD2 NM_018076.5 splice_region, intron
• Scores: Splicing: ADA: 0.5620
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.05
• Publications: 1 publications found

Genes affected

ODAD2 (HGNC:25583): (outer dynein arm docking complex subunit 2) The protein encoded by this gene contains ten Armadillo repeat motifs (ARMs) and one HEAT repeat, and is thought to be involved in ciliary and flagellar movement. This protein has been shown to localize to the ciliary axonemes and at the ciliary base of respiratory cells. Studies indicate that mutations in this gene cause partial outer dynein arm (ODA) defects in respiratory cilia. The cilia of cells with mutations in this gene displayed either reduced ciliary beat frequency and amplitude, or, complete immotility. Some individuals with primary ciliary dyskensia (PCD) have been shown to have mutations in this gene. PCD is characterized by chronic airway disease and left/right body asymmetry defects. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Aug 2015]

ODAD2 Gene-Disease associations (from GenCC):

• primary ciliary dyskinesia 23

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: G2P, ClinGen, Labcorp Genetics (formerly Invitae)
• primary ciliary dyskinesia

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Likely_benign. The variant received -6 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BP6: Variant 10-27971320-T-C is Benign according to our data. Variant chr10-27971320-T-C is described in ClinVar as Likely_benign. ClinVar VariationId is 474593.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ODAD2	NM_018076.5	c.937-7A>G		splice_region_variant, intron_variant	Intron 7 of 19	ENST00000305242.10	NP_060546.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ODAD2	ENST00000305242.10	c.937-7A>G		splice_region_variant, intron_variant	Intron 7 of 19	1	NM_018076.5	ENSP00000306410.5

Frequencies

GnomAD3 genomes AF: 0.000177 AC: 27 AN: 152180 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000965

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: 0.0000942

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000323

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000179 AC: 39 AN: 218028 AF XY: 0.000135

Gnomad AFR exome AF: 0.000132

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0000494

Gnomad NFE exome AF: 0.000339

Gnomad OTH exome AF: 0.000198

GnomAD4 exome AF: 0.000376 AC: 537 AN: 1426376 Hom.: 0 Cov.: 28 AF XY: 0.000362 AC XY: 257 AN XY: 709168

African (AFR) AF: 0.0000961 AC: 3 AN: 31204

American (AMR) AF: 0.00 AC: 0 AN: 35258

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24326

East Asian (EAS) AF: 0.00 AC: 0 AN: 39388

South Asian (SAS) AF: 0.00 AC: 0 AN: 79694

European-Finnish (FIN) AF: 0.0000191 AC: 1 AN: 52326

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5544

European-Non Finnish (NFE) AF: 0.000475 AC: 522 AN: 1099938

Other (OTH) AF: 0.000187 AC: 11 AN: 58698

GnomAD4 genome AF: 0.000177 AC: 27 AN: 152180 Hom.: 0 Cov.: 32 AF XY: 0.000161 AC XY: 12 AN XY: 74358

African (AFR) AF: 0.0000965 AC: 4 AN: 41430

American (AMR) AF: 0.00 AC: 0 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5196

South Asian (SAS) AF: 0.00 AC: 0 AN: 4838

European-Finnish (FIN) AF: 0.0000942 AC: 1 AN: 10612

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.000323 AC: 22 AN: 68036

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.000231 Hom.: 0

Bravo AF: 0.000166

EpiCase AF: 0.000276

EpiControl AF: 0.000240

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Primary ciliary dyskinesia 23 Benign:1

Jan 27, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	4.8
DANN	Benign	0.37
PhyloP100		-1.0

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.56
dbscSNV1_RF	Benign	0.40
SpliceAI score (max)		0.99		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.99		Position offset: -1
DS_AL_spliceai		0.97		Position offset: -7

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

Other links and lift over

dbSNP: rs370699691; hg19: chr10-28260249;