NM_023036.6:c.468-28C>T

Variant names:

• chr17-74289566-C-T
• rs62065706
• NM_023036.6:c.468-28C>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_023036.6(DNAI2):​c.468-28C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.147 in 1,612,230 control chromosomes in the GnomAD database, including 18,812 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.12 (1279 hom., cov: 31)
  • Exomes 𝑓: 0.15 (17533 hom.)
• Consequence: DNAI2 NM_023036.6 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.397
• 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

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant 17-74289566-C-T is Benign according to our data. Variant chr17-74289566-C-T is described in ClinVar as Benign. ClinVar VariationId is 261652.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.155 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.468-28C>T		intron	N/A	NP_075462.3	Q9GZS0-1
	DNAI2	NM_001353167.2		c.468-28C>T		intron	N/A	NP_001340096.1
	DNAI2	NM_001172810.3		c.468-28C>T		intron	N/A	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.468-28C>T		intron	N/A	ENSP00000308312.6	Q9GZS0-1
	DNAI2	ENST00000579490.5	TSL:1	c.639-28C>T		intron	N/A	ENSP00000464197.1	J3QRG2
	DNAI2	ENST00000446837.2	TSL:1	c.468-28C>T		intron	N/A	ENSP00000400252.2	Q9GZS0-1

Frequencies

GnomAD3 genomes AF: 0.121 AC: 18287 AN: 151466 Hom.: 1280 Cov.: 31

Gnomad AFR AF: 0.0774

Gnomad AMI AF: 0.115

Gnomad AMR AF: 0.0816

Gnomad ASJ AF: 0.118

Gnomad EAS AF: 0.00425

Gnomad SAS AF: 0.122

Gnomad FIN AF: 0.170

Gnomad MID AF: 0.0737

Gnomad NFE AF: 0.158

Gnomad OTH AF: 0.109

GnomAD2 exomes AF: 0.123 AC: 30851 AN: 250566 AF XY: 0.128

Gnomad AFR exome AF: 0.0804

Gnomad AMR exome AF: 0.0557

Gnomad ASJ exome AF: 0.108

Gnomad EAS exome AF: 0.00283

Gnomad FIN exome AF: 0.170

Gnomad NFE exome AF: 0.160

Gnomad OTH exome AF: 0.122

GnomAD4 exome AF: 0.150 AC: 219072 AN: 1460654 Hom.: 17533 Cov.: 35 AF XY: 0.150 AC XY: 109317 AN XY: 726656

African (AFR) AF: 0.0774 AC: 2589 AN: 33458

American (AMR) AF: 0.0579 AC: 2587 AN: 44702

Ashkenazi Jewish (ASJ) AF: 0.112 AC: 2924 AN: 26128

East Asian (EAS) AF: 0.00179 AC: 71 AN: 39696

South Asian (SAS) AF: 0.133 AC: 11486 AN: 86230

European-Finnish (FIN) AF: 0.171 AC: 9092 AN: 53110

Middle Eastern (MID) AF: 0.114 AC: 656 AN: 5758

European-Non Finnish (NFE) AF: 0.164 AC: 182091 AN: 1111212

Other (OTH) AF: 0.126 AC: 7576 AN: 60360

GnomAD4 genome AF: 0.121 AC: 18301 AN: 151576 Hom.: 1279 Cov.: 31 AF XY: 0.119 AC XY: 8813 AN XY: 73980

African (AFR) AF: 0.0775 AC: 3206 AN: 41374

American (AMR) AF: 0.0815 AC: 1240 AN: 15220

Ashkenazi Jewish (ASJ) AF: 0.118 AC: 409 AN: 3460

East Asian (EAS) AF: 0.00426 AC: 22 AN: 5162

South Asian (SAS) AF: 0.123 AC: 587 AN: 4780

European-Finnish (FIN) AF: 0.170 AC: 1760 AN: 10368

Middle Eastern (MID) AF: 0.0793 AC: 23 AN: 290

European-Non Finnish (NFE) AF: 0.158 AC: 10722 AN: 67906

Other (OTH) AF: 0.108 AC: 227 AN: 2106

Alfa AF: 0.141 Hom.: 494

Bravo AF: 0.112

Asia WGS AF: 0.0560 AC: 196 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	1.4
DANN	Benign	0.35
PhyloP100		0.40
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: rs62065706; hg19: chr17-72285705;