rs9908476

Variant names:

• chr17-74312152-C-A
• rs9908476
• NM_023036.6:c.1644C>A

Your query was ambiguous. Multiple possible variants found:

• chr17-74312152-C-A
• chr17-74312152-C-G
• chr17-74312152-C-T

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BA1

The NM_023036.6(DNAI2):​c.1644C>A​(p.Ala548Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0321 in 1,612,522 control chromosomes in the GnomAD database, including 954 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Synonymous variant affecting the same amino acid position (i.e. A548A) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.039 (126 hom., cov: 33)
  • Exomes 𝑓: 0.031 (828 hom.)
• Consequence: DNAI2 NM_023036.6 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:9
• Conservation: PhyloP100: -2.68
• Publications: 2 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

LOC105371891 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -19 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.43).
• BP6: Variant 17-74312152-C-A is Benign according to our data. Variant chr17-74312152-C-A is described in ClinVar as Benign. ClinVar VariationId is 163170.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-2.68 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0549 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.1644C>A	p.Ala548Ala	synonymous	Exon 12 of 14	NP_075462.3	Q9GZS0-1
	DNAI2	NM_001353167.2		c.1644C>A	p.Ala548Ala	synonymous	Exon 12 of 15	NP_001340096.1
	DNAI2	NM_001172810.3		c.1608C>A	p.Ala536Ala	synonymous	Exon 12 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.1644C>A	p.Ala548Ala	synonymous	Exon 12 of 14	ENSP00000308312.6	Q9GZS0-1
	DNAI2	ENST00000579490.5	TSL:1	c.1815C>A	p.Ala605Ala	synonymous	Exon 11 of 13	ENSP00000464197.1	J3QRG2
	DNAI2	ENST00000446837.2	TSL:1	c.1644C>A	p.Ala548Ala	synonymous	Exon 11 of 13	ENSP00000400252.2	Q9GZS0-1

Frequencies

GnomAD3 genomes AF: 0.0389 AC: 5891 AN: 151510 Hom.: 125 Cov.: 33

Gnomad AFR AF: 0.0567

Gnomad AMI AF: 0.0176

Gnomad AMR AF: 0.0320

Gnomad ASJ AF: 0.0346

Gnomad EAS AF: 0.000195

Gnomad SAS AF: 0.0332

Gnomad FIN AF: 0.0385

Gnomad MID AF: 0.0506

Gnomad NFE AF: 0.0332

Gnomad OTH AF: 0.0470

GnomAD2 exomes AF: 0.0312 AC: 7785 AN: 249636 AF XY: 0.0316

Gnomad AFR exome AF: 0.0574

Gnomad AMR exome AF: 0.0176

Gnomad ASJ exome AF: 0.0394

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0365

Gnomad NFE exome AF: 0.0339

Gnomad OTH exome AF: 0.0325

GnomAD4 exome AF: 0.0314 AC: 45845 AN: 1460894 Hom.: 828 Cov.: 32 AF XY: 0.0313 AC XY: 22780 AN XY: 726706

African (AFR) AF: 0.0582 AC: 1948 AN: 33446

American (AMR) AF: 0.0198 AC: 886 AN: 44690

Ashkenazi Jewish (ASJ) AF: 0.0383 AC: 1001 AN: 26116

East Asian (EAS) AF: 0.0000756 AC: 3 AN: 39662

South Asian (SAS) AF: 0.0357 AC: 3077 AN: 86224

European-Finnish (FIN) AF: 0.0355 AC: 1890 AN: 53244

Middle Eastern (MID) AF: 0.0547 AC: 311 AN: 5684

European-Non Finnish (NFE) AF: 0.0312 AC: 34644 AN: 1111524

Other (OTH) AF: 0.0346 AC: 2085 AN: 60304

GnomAD4 genome AF: 0.0389 AC: 5902 AN: 151628 Hom.: 126 Cov.: 33 AF XY: 0.0378 AC XY: 2800 AN XY: 74092

African (AFR) AF: 0.0568 AC: 2347 AN: 41340

American (AMR) AF: 0.0320 AC: 486 AN: 15208

Ashkenazi Jewish (ASJ) AF: 0.0346 AC: 120 AN: 3468

East Asian (EAS) AF: 0.000196 AC: 1 AN: 5108

South Asian (SAS) AF: 0.0328 AC: 157 AN: 4792

European-Finnish (FIN) AF: 0.0385 AC: 403 AN: 10466

Middle Eastern (MID) AF: 0.0544 AC: 16 AN: 294

European-Non Finnish (NFE) AF: 0.0332 AC: 2258 AN: 67936

Other (OTH) AF: 0.0465 AC: 98 AN: 2106

Alfa AF: 0.0278 Hom.: 38

Bravo AF: 0.0391

EpiCase AF: 0.0361

EpiControl AF: 0.0355

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.43
CADD	Benign	0.059
DANN	Benign	0.78
PhyloP100		-2.7
Mutation Taster		=100/0	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: rs9908476; hg19: chr17-72308291; COSMIC: COSV56758874; COSMIC: COSV56758874;