rs606231164

chr9-34489343-T-TAATA

Variant summary

Our verdict is Pathogenic. Variant got 11 ACMG points: 11P and 0B. PVS1 PM2 PP5

The NM_012144.4(DNAI1):c.282_283insAATA(p.Gly95AsnfsTer24) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (no stars). Synonymous variant affecting the same amino acid position (i.e. I94I) has been classified as Likely benign. Variant results in nonsense mediated mRNA decay.

• Frequency: Genomes: not found (cov: 32)
• Consequence: DNAI1 NM_012144.4 frameshift
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 2.85

Genes affected

DNAI1 (HGNC:2954): (dynein axonemal intermediate chain 1) This gene encodes a member of the dynein intermediate chain family. The encoded protein is part of the dynein complex in respiratory cilia. The inner- and outer-arm dyneins, which bridge between the doublet microtubules in axonemes, are the force-generating proteins responsible for the sliding movement in axonemes. The intermediate and light chains, thought to form the base of the dynein arm, help mediate attachment and may also participate in regulating dynein activity. Mutations in this gene result in abnormal ciliary ultrastructure and function associated with primary ciliary dyskinesia and Kartagener syndrome. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2013]

ACMG classification

Verdict is Pathogenic. Variant got 11 ACMG points.

• PVS1: Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 9-34489343-T-TAATA is Pathogenic according to our data. Variant chr9-34489343-T-TAATA is described in ClinVar as [Pathogenic]. Clinvar id is 5605.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DNAI1	NM_012144.4	c.282_283insAATA	p.Gly95AsnfsTer24	frameshift_variant	5/20	ENST00000242317.9
DNAI1	NM_001281428.2	c.282_283insAATA	p.Gly95AsnfsTer24	frameshift_variant	5/20

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DNAI1	ENST00000242317.9	c.282_283insAATA	p.Gly95AsnfsTer24	frameshift_variant	5/20	1	NM_012144.4
DNAI1	ENST00000437363.5	c.249_250insAATA	p.Gly84AsnfsTer24	frameshift_variant	4/9	5
DNAI1	ENST00000614641.4	c.282_283insAATA	p.Gly95AsnfsTer24	frameshift_variant	5/20	5		P1
DNAI1	ENST00000488369.1	n.398_399insAATA		non_coding_transcript_exon_variant	5/9	3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

Kartagener syndrome Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Dec 01, 1999

- -

Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs606231164; hg19: chr9-34489341;