chr17-74312264-G-C

Variant names:

• chr17-74312264-G-C
• rs4239008
• NM_023036.6:c.1722+34G>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_023036.6(DNAI2):​c.1722+34G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000112 in 357,804 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 26)
  • Exomes 𝑓: 0.000011 (0 hom.)
• Consequence: DNAI2 NM_023036.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.201
• Publications: 5 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

ENSG00000309634 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAI2	NM_023036.6	MANE Select	c.1722+34G>C		intron	N/A	NP_075462.3
	DNAI2	NM_001353167.2		c.1722+34G>C		intron	N/A	NP_001340096.1
	DNAI2	NM_001172810.3		c.1686+34G>C		intron	N/A	NP_001166281.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAI2	ENST00000311014.11	TSL:1 MANE Select	c.1722+34G>C		intron	N/A	ENSP00000308312.6
	DNAI2	ENST00000579490.5	TSL:1	c.1893+34G>C		intron	N/A	ENSP00000464197.1
	DNAI2	ENST00000446837.2	TSL:1	c.1722+34G>C		intron	N/A	ENSP00000400252.2

Frequencies

GnomAD3 genomes Cov.: 26

GnomAD4 exome AF: 0.0000112 AC: 4 AN: 357804 Hom.: 0 Cov.: 0 AF XY: 0.0000153 AC XY: 3 AN XY: 195944

African (AFR) AF: 0.000211 AC: 2 AN: 9496

American (AMR) AF: 0.00 AC: 0 AN: 26688

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 12726

East Asian (EAS) AF: 0.00 AC: 0 AN: 15732

South Asian (SAS) AF: 0.00 AC: 0 AN: 59904

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 31002

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1876

European-Non Finnish (NFE) AF: 0.0000109 AC: 2 AN: 183366

Other (OTH) AF: 0.00 AC: 0 AN: 17014

GnomAD4 genome Cov.: 26

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	5.8
DANN	Benign	0.70
PhyloP100		0.20

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: rs4239008; hg19: chr17-72308403;