rs62065707

chr17-74289767-G-A

Variant summary

Our verdict is Benign. Variant got -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:3
• Conservation: PhyloP100: 0.918

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]

ACMG classification

Verdict is Benign. Variant got -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 id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DNAI2	NM_023036.6	c.610+31G>A		intron_variant		ENST00000311014.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DNAI2	ENST00000311014.11	c.610+31G>A		intron_variant		1	NM_023036.6	P2

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

GnomAD3 exomes AF: 0.124 AC: 30944 AN: 250198 Hom.: 2319 AF XY: 0.128 AC XY: 17347 AN XY: 135262

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 SAS exome AF: 0.131

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

Gnomad4 AFR exome AF: 0.0773

Gnomad4 AMR exome AF: 0.0581

Gnomad4 ASJ exome AF: 0.112

Gnomad4 EAS exome AF: 0.00136

Gnomad4 SAS exome AF: 0.133

Gnomad4 FIN exome AF: 0.172

Gnomad4 NFE exome AF: 0.164

Gnomad4 OTH exome AF: 0.126

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

Gnomad4 AFR AF: 0.0780

Gnomad4 AMR AF: 0.0821

Gnomad4 ASJ AF: 0.119

Gnomad4 EAS AF: 0.00368

Gnomad4 SAS AF: 0.124

Gnomad4 FIN AF: 0.172

Gnomad4 NFE AF: 0.158

Gnomad4 OTH AF: 0.107

Alfa AF: 0.140 Hom.: 283

Bravo AF: 0.112

Asia WGS AF: 0.0560 AC: 197 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

-

- -

Primary ciliary dyskinesia 9 Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 10, 2021

- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 11, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
Cadd	Benign	7.6
Dann	Benign	0.65

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

Publications

LitVar

Other links and lift over

dbSNP: rs62065707; hg19: chr17-72285906;