rs4239008

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

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

Variant summary

Our verdict is Benign. The variant received -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:4
• 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: ClinGen, Labcorp Genetics (formerly Invitae)
• primary ciliary dyskinesia

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ENSG00000309634 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAI2	NM_023036.6	MANE Select	c.1722+34G>A		intron	N/A	NP_075462.3	Q9GZS0-1
	DNAI2	NM_001353167.2		c.1722+34G>A		intron	N/A	NP_001340096.1
	DNAI2	NM_001172810.3		c.1686+34G>A		intron	N/A	NP_001166281.1	Q9GZS0-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAI2	ENST00000311014.11	TSL:1 MANE Select	c.1722+34G>A		intron	N/A	ENSP00000308312.6	Q9GZS0-1
	DNAI2	ENST00000579490.5	TSL:1	c.1893+34G>A		intron	N/A	ENSP00000464197.1	J3QRG2
	DNAI2	ENST00000446837.2	TSL:1	c.1722+34G>A		intron	N/A	ENSP00000400252.2	Q9GZS0-1

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

GnomAD2 exomes AF: 0.867 AC: 124824 AN: 144000 AF XY: 0.869

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 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

African (AFR) AF: 0.432 AC: 4094 AN: 9486

American (AMR) AF: 0.926 AC: 24708 AN: 26680

Ashkenazi Jewish (ASJ) AF: 0.882 AC: 11206 AN: 12712

East Asian (EAS) AF: 0.844 AC: 13258 AN: 15708

South Asian (SAS) AF: 0.833 AC: 49885 AN: 59888

European-Finnish (FIN) AF: 0.891 AC: 27578 AN: 30964

Middle Eastern (MID) AF: 0.855 AC: 1604 AN: 1876

European-Non Finnish (NFE) AF: 0.905 AC: 165949 AN: 183278

Other (OTH) AF: 0.855 AC: 14531 AN: 16994

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

African (AFR) AF: 0.438 AC: 17536 AN: 40056

American (AMR) AF: 0.881 AC: 13111 AN: 14886

Ashkenazi Jewish (ASJ) AF: 0.890 AC: 3080 AN: 3462

East Asian (EAS) AF: 0.845 AC: 4154 AN: 4916

South Asian (SAS) AF: 0.833 AC: 3913 AN: 4696

European-Finnish (FIN) AF: 0.880 AC: 8582 AN: 9750

Middle Eastern (MID) AF: 0.837 AC: 246 AN: 294

European-Non Finnish (NFE) AF: 0.905 AC: 61294 AN: 67700

Other (OTH) AF: 0.786 AC: 1643 AN: 2090

Alfa AF: 0.803 Hom.: 6470

Asia WGS AF: 0.804 AC: 2792 AN: 3476

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	not specified (1)
-	-	1	Primary ciliary dyskinesia 9 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	6.2
DANN	Benign	0.75
PhyloP100		0.20
Mutation Taster		=21/79	disease causing

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;