NM_001364171.2:c.2019T>C

Variant names:

• chr19-48297081-A-G
• rs7252988
• NM_001364171.2:c.2019T>C

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_001364171.2(ODAD1):​c.2019T>C​(p.Ser673Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.633 in 1,613,386 control chromosomes in the GnomAD database, including 331,731 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.59 (27177 hom., cov: 32)
  • Exomes 𝑓: 0.64 (304554 hom.)
• Consequence: ODAD1 NM_001364171.2 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:7
• Conservation: PhyloP100: -8.96
• Publications: 18 publications found

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]

ODAD1 Gene-Disease associations (from GenCC):

• primary ciliary dyskinesia 20

  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: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.1).
• BP6: Variant 19-48297081-A-G is Benign according to our data. Variant chr19-48297081-A-G is described in ClinVar as Benign. ClinVar VariationId is 262496.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-8.96 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.668 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001364171.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ODAD1	NM_001364171.2	MANE Select	c.2019T>C	p.Ser673Ser	synonymous	Exon 16 of 16	NP_001351100.1	A0A6I8PTZ2
	ODAD1	NM_144577.4		c.1908T>C	p.Ser636Ser	synonymous	Exon 14 of 14	NP_653178.3	Q96M63-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ODAD1	ENST00000674294.1	MANE Select	c.2019T>C	p.Ser673Ser	synonymous	Exon 16 of 16	ENSP00000501363.1	A0A6I8PTZ2
	ODAD1	ENST00000315396.7	TSL:1	c.1908T>C	p.Ser636Ser	synonymous	Exon 14 of 14	ENSP00000318429.7	Q96M63-1
	ODAD1	ENST00000859784.1		c.2079T>C	p.Ser693Ser	synonymous	Exon 15 of 15	ENSP00000529843.1

Frequencies

GnomAD3 genomes AF: 0.589 AC: 89502 AN: 151870 Hom.: 27159 Cov.: 32

Gnomad AFR AF: 0.529

Gnomad AMI AF: 0.514

Gnomad AMR AF: 0.497

Gnomad ASJ AF: 0.653

Gnomad EAS AF: 0.269

Gnomad SAS AF: 0.454

Gnomad FIN AF: 0.619

Gnomad MID AF: 0.630

Gnomad NFE AF: 0.674

Gnomad OTH AF: 0.598

GnomAD2 exomes AF: 0.563 AC: 141230 AN: 250780 AF XY: 0.570

Gnomad AFR exome AF: 0.523

Gnomad AMR exome AF: 0.391

Gnomad ASJ exome AF: 0.669

Gnomad EAS exome AF: 0.269

Gnomad FIN exome AF: 0.617

Gnomad NFE exome AF: 0.673

Gnomad OTH exome AF: 0.596

GnomAD4 exome AF: 0.638 AC: 931918 AN: 1461398 Hom.: 304554 Cov.: 71 AF XY: 0.633 AC XY: 460424 AN XY: 727046

African (AFR) AF: 0.527 AC: 17628 AN: 33476

American (AMR) AF: 0.403 AC: 18023 AN: 44718

Ashkenazi Jewish (ASJ) AF: 0.669 AC: 17480 AN: 26130

East Asian (EAS) AF: 0.253 AC: 10060 AN: 39698

South Asian (SAS) AF: 0.467 AC: 40304 AN: 86254

European-Finnish (FIN) AF: 0.618 AC: 32789 AN: 53060

Middle Eastern (MID) AF: 0.595 AC: 3422 AN: 5754

European-Non Finnish (NFE) AF: 0.679 AC: 754947 AN: 1111930

Other (OTH) AF: 0.617 AC: 37265 AN: 60378

GnomAD4 genome AF: 0.589 AC: 89566 AN: 151988 Hom.: 27177 Cov.: 32 AF XY: 0.581 AC XY: 43151 AN XY: 74280

African (AFR) AF: 0.529 AC: 21935 AN: 41460

American (AMR) AF: 0.496 AC: 7579 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.653 AC: 2267 AN: 3472

East Asian (EAS) AF: 0.268 AC: 1379 AN: 5138

South Asian (SAS) AF: 0.454 AC: 2188 AN: 4816

European-Finnish (FIN) AF: 0.619 AC: 6546 AN: 10578

Middle Eastern (MID) AF: 0.629 AC: 185 AN: 294

European-Non Finnish (NFE) AF: 0.674 AC: 45763 AN: 67938

Other (OTH) AF: 0.595 AC: 1255 AN: 2110

Alfa AF: 0.642 Hom.: 45411

Bravo AF: 0.577

Asia WGS AF: 0.359 AC: 1253 AN: 3478

EpiCase AF: 0.667

EpiControl AF: 0.664

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not specified (3)
-	-	2	not provided (2)
-	-	2	Primary ciliary dyskinesia (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.1
CADD	Benign	0.022
DANN	Benign	0.36
PhyloP100		-9.0
Mutation Taster		=99/1	polymorphism (auto)

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: rs7252988; hg19: chr19-48800338; COSMIC: COSV59555559;