17-74305284-G-A

Variant names:

• chr17-74305284-G-A
• rs34392071
• NM_023036.6:c.1053G>A
• DNAI2 p.Thr351Thr

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.1053G>A​(p.Thr351Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00861 in 1,614,122 control chromosomes in the GnomAD database, including 996 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.045 (501 hom., cov: 32)
  • Exomes 𝑓: 0.0048 (495 hom.)
• Consequence: DNAI2 NM_023036.6 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:9
• Conservation: PhyloP100: -5.00
• Publications: 3 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=-0.75).
• BP6: Variant 17-74305284-G-A is Benign according to our data. Variant chr17-74305284-G-A is described in ClinVar as Benign. ClinVar VariationId is 261638.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-5 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.152 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.1053G>A	p.Thr351Thr	synonymous	Exon 9 of 14	NP_075462.3	Q9GZS0-1
	DNAI2	NM_001353167.2		c.1053G>A	p.Thr351Thr	synonymous	Exon 9 of 15	NP_001340096.1
	DNAI2	NM_001172810.3		c.1053G>A	p.Thr351Thr	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.1053G>A	p.Thr351Thr	synonymous	Exon 9 of 14	ENSP00000308312.6	Q9GZS0-1
	DNAI2	ENST00000579490.5	TSL:1	c.1224G>A	p.Thr408Thr	synonymous	Exon 8 of 13	ENSP00000464197.1	J3QRG2
	DNAI2	ENST00000446837.2	TSL:1	c.1053G>A	p.Thr351Thr	synonymous	Exon 8 of 13	ENSP00000400252.2	Q9GZS0-1

Frequencies

GnomAD3 genomes AF: 0.0450 AC: 6842 AN: 152116 Hom.: 498 Cov.: 32

Gnomad AFR AF: 0.155

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0196

Gnomad ASJ AF: 0.000865

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000622

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.000603

Gnomad OTH AF: 0.0354

GnomAD2 exomes AF: 0.0122 AC: 3072 AN: 251478 AF XY: 0.00895

Gnomad AFR exome AF: 0.167

Gnomad AMR exome AF: 0.00697

Gnomad ASJ exome AF: 0.00109

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000536

Gnomad OTH exome AF: 0.00570

GnomAD4 exome AF: 0.00482 AC: 7041 AN: 1461888 Hom.: 495 Cov.: 30 AF XY: 0.00412 AC XY: 2995 AN XY: 727246

African (AFR) AF: 0.162 AC: 5433 AN: 33478

American (AMR) AF: 0.00818 AC: 366 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00134 AC: 35 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.000359 AC: 31 AN: 86258

European-Finnish (FIN) AF: 0.0000187 AC: 1 AN: 53420

Middle Eastern (MID) AF: 0.0111 AC: 64 AN: 5768

European-Non Finnish (NFE) AF: 0.000344 AC: 383 AN: 1112010

Other (OTH) AF: 0.0121 AC: 728 AN: 60396

GnomAD4 genome AF: 0.0450 AC: 6850 AN: 152234 Hom.: 501 Cov.: 32 AF XY: 0.0424 AC XY: 3157 AN XY: 74448

African (AFR) AF: 0.155 AC: 6429 AN: 41498

American (AMR) AF: 0.0195 AC: 299 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.000865 AC: 3 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.000622 AC: 3 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10614

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.000603 AC: 41 AN: 68026

Other (OTH) AF: 0.0350 AC: 74 AN: 2112

Alfa AF: 0.0134 Hom.: 115

Bravo AF: 0.0522

Asia WGS AF: 0.00953 AC: 34 AN: 3478

EpiCase AF: 0.000491

EpiControl AF: 0.000474

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)
-	-	2	not provided (2)
-	-	1	Primary ciliary dyskinesia 9 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	0.14
DANN	Benign	0.88
PhyloP100		-5.0
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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs34392071;

hg19: chr17-72301423;