rs62065707

Variant names:

• chr17-74289767-G-A
• rs62065707
• NM_023036.6:c.610+31G>A

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.610+31G>A 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 1,612,864 control chromosomes in the GnomAD database, including 18,846 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.12 (1290 hom., cov: 31)
  • Exomes 𝑓: 0.15 (17556 hom.)
• Consequence: DNAI2 NM_023036.6 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 0.918
• Publications: 4 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=-0.81).
• BP6: Variant 17-74289767-G-A is Benign according to our data. Variant chr17-74289767-G-A is described in ClinVar as Benign. ClinVar VariationId is 261653.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.156 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.610+31G>A		intron	N/A	NP_075462.3	Q9GZS0-1
	DNAI2	NM_001353167.2		c.610+31G>A		intron	N/A	NP_001340096.1
	DNAI2	NM_001172810.3		c.610+31G>A		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.610+31G>A		intron	N/A	ENSP00000308312.6	Q9GZS0-1
	DNAI2	ENST00000579490.5	TSL:1	c.781+31G>A		intron	N/A	ENSP00000464197.1	J3QRG2
	DNAI2	ENST00000446837.2	TSL:1	c.610+31G>A		intron	N/A	ENSP00000400252.2	Q9GZS0-1

Frequencies

GnomAD3 genomes AF: 0.121 AC: 18417 AN: 151924 Hom.: 1291 Cov.: 31

Gnomad AFR AF: 0.0779

Gnomad AMI AF: 0.115

Gnomad AMR AF: 0.0823

Gnomad ASJ AF: 0.119

Gnomad EAS AF: 0.00367

Gnomad SAS AF: 0.123

Gnomad FIN AF: 0.172

Gnomad MID AF: 0.0791

Gnomad NFE AF: 0.158

Gnomad OTH AF: 0.108

GnomAD2 exomes AF: 0.124 AC: 30944 AN: 250198 AF XY: 0.128

Gnomad AFR exome AF: 0.0804

Gnomad AMR exome AF: 0.0559

Gnomad ASJ exome AF: 0.108

Gnomad EAS exome AF: 0.00283

Gnomad FIN exome AF: 0.173

Gnomad NFE exome AF: 0.161

Gnomad OTH exome AF: 0.123

GnomAD4 exome AF: 0.150 AC: 219409 AN: 1460822 Hom.: 17556 Cov.: 35 AF XY: 0.151 AC XY: 109452 AN XY: 726686

African (AFR) AF: 0.0773 AC: 2589 AN: 33472

American (AMR) AF: 0.0581 AC: 2597 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.112 AC: 2926 AN: 26132

East Asian (EAS) AF: 0.00136 AC: 54 AN: 39692

South Asian (SAS) AF: 0.133 AC: 11499 AN: 86238

European-Finnish (FIN) AF: 0.172 AC: 9071 AN: 52804

Middle Eastern (MID) AF: 0.114 AC: 653 AN: 5720

European-Non Finnish (NFE) AF: 0.164 AC: 182434 AN: 1111676

Other (OTH) AF: 0.126 AC: 7586 AN: 60368

GnomAD4 genome AF: 0.121 AC: 18431 AN: 152042 Hom.: 1290 Cov.: 31 AF XY: 0.120 AC XY: 8915 AN XY: 74334

African (AFR) AF: 0.0780 AC: 3236 AN: 41492

American (AMR) AF: 0.0821 AC: 1254 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.119 AC: 411 AN: 3468

East Asian (EAS) AF: 0.00368 AC: 19 AN: 5166

South Asian (SAS) AF: 0.124 AC: 596 AN: 4814

European-Finnish (FIN) AF: 0.172 AC: 1821 AN: 10572

Middle Eastern (MID) AF: 0.0850 AC: 25 AN: 294

European-Non Finnish (NFE) AF: 0.158 AC: 10740 AN: 67950

Other (OTH) AF: 0.107 AC: 225 AN: 2108

Alfa AF: 0.138 Hom.: 284

Bravo AF: 0.112

Asia WGS AF: 0.0560 AC: 197 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)
-	-	1	Primary ciliary dyskinesia 9 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	7.6
DANN	Benign	0.65
PhyloP100		0.92
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: rs62065707; hg19: chr17-72285906;