rs117075898

Variant names:

• chr17-74301028-C-T
• rs117075898
• NM_023036.6:c.865-18C>T

Your query was ambiguous. Multiple possible variants found:

• chr17-74301028-C-T
• chr17-74301028-C-A
• chr17-74301028-C-G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_023036.6(DNAI2):​c.865-18C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00163 in 1,613,392 control chromosomes in the GnomAD database, including 19 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0046 (9 hom., cov: 31)
  • Exomes 𝑓: 0.0013 (10 hom.)
• Consequence: DNAI2 NM_023036.6 intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -2.44
• Publications: 1 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

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 17-74301028-C-T is Benign according to our data. Variant chr17-74301028-C-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 261657.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00461 (702/152222) while in subpopulation AFR AF = 0.013 (541/41516). AF 95% confidence interval is 0.0121. There are 9 homozygotes in GnomAd4. There are 340 alleles in the male GnomAd4 subpopulation. Median coverage is 31. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 9 AR,AD gene

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.865-18C>T		intron	N/A	NP_075462.3	Q9GZS0-1
	DNAI2	NM_001353167.2		c.865-18C>T		intron	N/A	NP_001340096.1
	DNAI2	NM_001172810.3		c.865-18C>T		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.865-18C>T		intron	N/A	ENSP00000308312.6	Q9GZS0-1
	DNAI2	ENST00000579490.5	TSL:1	c.1036-18C>T		intron	N/A	ENSP00000464197.1	J3QRG2
	DNAI2	ENST00000446837.2	TSL:1	c.865-18C>T		intron	N/A	ENSP00000400252.2	Q9GZS0-1

Frequencies

GnomAD3 genomes AF: 0.00460 AC: 700 AN: 152104 Hom.: 9 Cov.: 31

Gnomad AFR AF: 0.0130

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00197

Gnomad ASJ AF: 0.0101

Gnomad EAS AF: 0.0125

Gnomad SAS AF: 0.00249

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000191

Gnomad OTH AF: 0.00239

GnomAD2 exomes AF: 0.00267 AC: 670 AN: 251314 AF XY: 0.00238

Gnomad AFR exome AF: 0.0152

Gnomad AMR exome AF: 0.00104

Gnomad ASJ exome AF: 0.00854

Gnomad EAS exome AF: 0.0104

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000202

Gnomad OTH exome AF: 0.00130

GnomAD4 exome AF: 0.00132 AC: 1931 AN: 1461170 Hom.: 10 Cov.: 32 AF XY: 0.00134 AC XY: 972 AN XY: 726882

African (AFR) AF: 0.0125 AC: 420 AN: 33468

American (AMR) AF: 0.00114 AC: 51 AN: 44690

Ashkenazi Jewish (ASJ) AF: 0.00835 AC: 218 AN: 26112

East Asian (EAS) AF: 0.0179 AC: 710 AN: 39670

South Asian (SAS) AF: 0.00274 AC: 236 AN: 86188

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53322

Middle Eastern (MID) AF: 0.00280 AC: 16 AN: 5712

European-Non Finnish (NFE) AF: 0.000112 AC: 124 AN: 1111672

Other (OTH) AF: 0.00259 AC: 156 AN: 60336

GnomAD4 genome AF: 0.00461 AC: 702 AN: 152222 Hom.: 9 Cov.: 31 AF XY: 0.00457 AC XY: 340 AN XY: 74440

African (AFR) AF: 0.0130 AC: 541 AN: 41516

American (AMR) AF: 0.00196 AC: 30 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.0101 AC: 35 AN: 3470

East Asian (EAS) AF: 0.0127 AC: 66 AN: 5186

South Asian (SAS) AF: 0.00249 AC: 12 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10616

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000191 AC: 13 AN: 68012

Other (OTH) AF: 0.00237 AC: 5 AN: 2110

Alfa AF: 0.00191 Hom.: 0

Bravo AF: 0.00542

Asia WGS AF: 0.00895 AC: 31 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.028
DANN	Benign	0.55
PhyloP100		-2.4
Mutation Taster		=100/0	polymorphism

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: rs117075898; hg19: chr17-72297167;