rs4239008

Positions:

• chr17-74312264-G-A
• chr17-74312264-G-C

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.1722+34G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.844 in 506,342 control chromosomes in the GnomAD database, including 185,208 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.77 (47068 hom., cov: 26)
  • Exomes 𝑓: 0.87 (138140 hom.)
• Consequence: DNAI2 NM_023036.6 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.201

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]

LOC105371891 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 17-74312264-G-A is Benign according to our data. Variant chr17-74312264-G-A is described in ClinVar as [Benign]. Clinvar id is 261645.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.899 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DNAI2	NM_023036.6	c.1722+34G>A		intron_variant		ENST00000311014.11
LOC105371891	XR_934971.3	n.277-79C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DNAI2	ENST00000311014.11	c.1722+34G>A		intron_variant		1	NM_023036.6	P2

Frequencies

GnomAD3 genomes AF: 0.769 AC: 114346 AN: 148656 Hom.: 47065 Cov.: 26

Gnomad AFR AF: 0.438

Gnomad AMI AF: 0.881

Gnomad AMR AF: 0.881

Gnomad ASJ AF: 0.890

Gnomad EAS AF: 0.845

Gnomad SAS AF: 0.833

Gnomad FIN AF: 0.880

Gnomad MID AF: 0.842

Gnomad NFE AF: 0.905

Gnomad OTH AF: 0.788

GnomAD3 exomes AF: 0.867 AC: 124824 AN: 144000 Hom.: 55094 AF XY: 0.869 AC XY: 67548 AN XY: 77774

Gnomad AFR exome AF: 0.415

Gnomad AMR exome AF: 0.929

Gnomad ASJ exome AF: 0.884

Gnomad EAS exome AF: 0.852

Gnomad SAS exome AF: 0.833

Gnomad FIN exome AF: 0.889

Gnomad NFE exome AF: 0.910

Gnomad OTH exome AF: 0.883

GnomAD4 exome AF: 0.875 AC: 312813 AN: 357586 Hom.: 138140 Cov.: 0 AF XY: 0.874 AC XY: 171097 AN XY: 195840

Gnomad4 AFR exome AF: 0.432

Gnomad4 AMR exome AF: 0.926

Gnomad4 ASJ exome AF: 0.882

Gnomad4 EAS exome AF: 0.844

Gnomad4 SAS exome AF: 0.833

Gnomad4 FIN exome AF: 0.891

Gnomad4 NFE exome AF: 0.905

Gnomad4 OTH exome AF: 0.855

GnomAD4 genome AF: 0.769 AC: 114357 AN: 148756 Hom.: 47068 Cov.: 26 AF XY: 0.771 AC XY: 55803 AN XY: 72336

Gnomad4 AFR AF: 0.438

Gnomad4 AMR AF: 0.881

Gnomad4 ASJ AF: 0.890

Gnomad4 EAS AF: 0.845

Gnomad4 SAS AF: 0.833

Gnomad4 FIN AF: 0.880

Gnomad4 NFE AF: 0.905

Gnomad4 OTH AF: 0.786

Alfa AF: 0.818 Hom.: 6398

Asia WGS AF: 0.804 AC: 2792 AN: 3476

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	-0.85
CADD	Benign	6.2
DANN	Benign	0.75

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: rs4239008; hg19: chr17-72308403;