rs8073660

Variant names:

• chr17-74305293-A-G
• rs8073660
• NM_023036.6:c.1062A>G

Your query was ambiguous. Multiple possible variants found:

• chr17-74305293-A-G
• chr17-74305293-A-C
• chr17-74305293-A-T

Variant summary

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

The NM_023036.6(DNAI2):​c.1062A>G​(p.Glu354Glu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.585 in 1,613,914 control chromosomes in the GnomAD database, including 284,557 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.50 (20533 hom., cov: 32)
  • Exomes 𝑓: 0.59 (264024 hom.)
• Consequence: DNAI2 NM_023036.6 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:11
• Conservation: PhyloP100: 2.14
• Publications: 23 publications found

Genes affected

DNAI2 (HGNC:18744): (dynein axonemal intermediate chain 2) The protein encoded by this gene belongs to the dynein intermediate chain family, and is part of the dynein complex of respiratory cilia and sperm flagella. Mutations in this gene are associated with primary ciliary dyskinesia type 9. Alternatively spliced transcript variants encoding different isoforms have been noted for this gene. [provided by RefSeq, Mar 2010]

DNAI2 Gene-Disease associations (from GenCC):

• primary ciliary dyskinesia 9

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: 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=-0.52).
• BP6: Variant 17-74305293-A-G is Benign according to our data. Variant chr17-74305293-A-G is described in ClinVar as Benign. ClinVar VariationId is 163168.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=2.14 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.621 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_023036.6. 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
	DNAI2	NM_023036.6	MANE Select	c.1062A>G	p.Glu354Glu	synonymous	Exon 9 of 14	NP_075462.3	Q9GZS0-1
	DNAI2	NM_001353167.2		c.1062A>G	p.Glu354Glu	synonymous	Exon 9 of 15	NP_001340096.1
	DNAI2	NM_001172810.3		c.1062A>G	p.Glu354Glu	synonymous	Exon 9 of 14	NP_001166281.1	Q9GZS0-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAI2	ENST00000311014.11	TSL:1 MANE Select	c.1062A>G	p.Glu354Glu	synonymous	Exon 9 of 14	ENSP00000308312.6	Q9GZS0-1
	DNAI2	ENST00000579490.5	TSL:1	c.1233A>G	p.Glu411Glu	synonymous	Exon 8 of 13	ENSP00000464197.1	J3QRG2
	DNAI2	ENST00000446837.2	TSL:1	c.1062A>G	p.Glu354Glu	synonymous	Exon 8 of 13	ENSP00000400252.2	Q9GZS0-1

Frequencies

GnomAD3 genomes AF: 0.505 AC: 76674 AN: 151922 Hom.: 20532 Cov.: 32

Gnomad AFR AF: 0.349

Gnomad AMI AF: 0.578

Gnomad AMR AF: 0.410

Gnomad ASJ AF: 0.530

Gnomad EAS AF: 0.256

Gnomad SAS AF: 0.508

Gnomad FIN AF: 0.580

Gnomad MID AF: 0.418

Gnomad NFE AF: 0.626

Gnomad OTH AF: 0.487

GnomAD2 exomes AF: 0.516 AC: 129774 AN: 251462 AF XY: 0.531

Gnomad AFR exome AF: 0.349

Gnomad AMR exome AF: 0.327

Gnomad ASJ exome AF: 0.527

Gnomad EAS exome AF: 0.248

Gnomad FIN exome AF: 0.591

Gnomad NFE exome AF: 0.623

Gnomad OTH exome AF: 0.538

GnomAD4 exome AF: 0.593 AC: 867065 AN: 1461874 Hom.: 264024 Cov.: 69 AF XY: 0.593 AC XY: 431264 AN XY: 727236

African (AFR) AF: 0.340 AC: 11397 AN: 33476

American (AMR) AF: 0.338 AC: 15124 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.526 AC: 13736 AN: 26136

East Asian (EAS) AF: 0.262 AC: 10385 AN: 39700

South Asian (SAS) AF: 0.522 AC: 45030 AN: 86258

European-Finnish (FIN) AF: 0.595 AC: 31811 AN: 53420

Middle Eastern (MID) AF: 0.474 AC: 2732 AN: 5768

European-Non Finnish (NFE) AF: 0.633 AC: 703885 AN: 1111996

Other (OTH) AF: 0.546 AC: 32965 AN: 60396

GnomAD4 genome AF: 0.504 AC: 76682 AN: 152040 Hom.: 20533 Cov.: 32 AF XY: 0.498 AC XY: 36981 AN XY: 74312

African (AFR) AF: 0.348 AC: 14451 AN: 41470

American (AMR) AF: 0.410 AC: 6258 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.530 AC: 1839 AN: 3470

East Asian (EAS) AF: 0.255 AC: 1312 AN: 5140

South Asian (SAS) AF: 0.510 AC: 2462 AN: 4828

European-Finnish (FIN) AF: 0.580 AC: 6130 AN: 10574

Middle Eastern (MID) AF: 0.408 AC: 120 AN: 294

European-Non Finnish (NFE) AF: 0.626 AC: 42562 AN: 67968

Other (OTH) AF: 0.486 AC: 1022 AN: 2104

Alfa AF: 0.579 Hom.: 116192

Bravo AF: 0.483

Asia WGS AF: 0.373 AC: 1303 AN: 3478

EpiCase AF: 0.607

EpiControl AF: 0.615

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not specified (3)
-	-	3	Primary ciliary dyskinesia (3)
-	-	3	Primary ciliary dyskinesia 9 (3)
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.52
CADD	Benign	8.3
DANN	Benign	0.75
PhyloP100		2.1
Mutation Taster		=91/9	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: rs8073660; hg19: chr17-72301432; COSMIC: COSV56759126; COSMIC: COSV56759126;