rs35732837

Variant names:

• chr17-74309977-CCT-C
• rs35732837
• NM_023036.6:c.1348-34_1348-33delTC

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_023036.6(DNAI2):​c.1348-34_1348-33delTC variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.899 in 1,612,936 control chromosomes in the GnomAD database, including 661,008 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.78 (50201 hom., cov: 0)
  • Exomes 𝑓: 0.91 (610807 hom.)
• Consequence: DNAI2 NM_023036.6 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0410
• 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: PanelApp Australia, Labcorp Genetics (formerly Invitae), ClinGen
• primary ciliary dyskinesia

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ENSG00000266106 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP6: Variant 17-74309977-CCT-C is Benign according to our data. Variant chr17-74309977-CCT-C is described in ClinVar as Likely_benign. ClinVar VariationId is 261640.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.92 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNAI2	NM_023036.6	c.1348-34_1348-33delTC		intron_variant	Intron 10 of 13	ENST00000311014.11	NP_075462.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DNAI2	ENST00000311014.11	c.1348-39_1348-38delCT		intron_variant	Intron 10 of 13	1	NM_023036.6	ENSP00000308312.6

Frequencies

GnomAD3 genomes AF: 0.785 AC: 119062 AN: 151746 Hom.: 50197 Cov.: 0

Gnomad AFR AF: 0.441

Gnomad AMI AF: 0.881

Gnomad AMR AF: 0.887

Gnomad ASJ AF: 0.905

Gnomad EAS AF: 0.931

Gnomad SAS AF: 0.871

Gnomad FIN AF: 0.898

Gnomad MID AF: 0.876

Gnomad NFE AF: 0.927

Gnomad OTH AF: 0.803

GnomAD2 exomes AF: 0.885 AC: 221102 AN: 249966 AF XY: 0.890

Gnomad AFR exome AF: 0.420

Gnomad AMR exome AF: 0.940

Gnomad ASJ exome AF: 0.897

Gnomad EAS exome AF: 0.933

Gnomad FIN exome AF: 0.903

Gnomad NFE exome AF: 0.925

Gnomad OTH exome AF: 0.898

GnomAD4 exome AF: 0.911 AC: 1330783 AN: 1461072 Hom.: 610807 AF XY: 0.911 AC XY: 662209 AN XY: 726838

African (AFR) AF: 0.423 AC: 14176 AN: 33478

American (AMR) AF: 0.933 AC: 41749 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.900 AC: 23510 AN: 26136

East Asian (EAS) AF: 0.925 AC: 36717 AN: 39698

South Asian (SAS) AF: 0.867 AC: 74817 AN: 86246

European-Finnish (FIN) AF: 0.908 AC: 47866 AN: 52728

Middle Eastern (MID) AF: 0.863 AC: 4977 AN: 5768

European-Non Finnish (NFE) AF: 0.930 AC: 1033646 AN: 1111906

Other (OTH) AF: 0.883 AC: 53325 AN: 60388

GnomAD4 genome AF: 0.784 AC: 119082 AN: 151864 Hom.: 50201 Cov.: 0 AF XY: 0.787 AC XY: 58450 AN XY: 74234

African (AFR) AF: 0.441 AC: 18214 AN: 41326

American (AMR) AF: 0.887 AC: 13536 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.905 AC: 3139 AN: 3470

East Asian (EAS) AF: 0.931 AC: 4800 AN: 5156

South Asian (SAS) AF: 0.871 AC: 4199 AN: 4820

European-Finnish (FIN) AF: 0.898 AC: 9494 AN: 10578

Middle Eastern (MID) AF: 0.873 AC: 255 AN: 292

European-Non Finnish (NFE) AF: 0.927 AC: 62961 AN: 67952

Other (OTH) AF: 0.801 AC: 1682 AN: 2100

Alfa AF: 0.866 Hom.: 10674

Bravo AF: 0.769

Asia WGS AF: 0.860 AC: 2990 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

-

PreventionGenetics, part of Exact Sciences

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.041
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.13		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: rs35732837; hg19: chr17-72306116;