NM_023036.6:c.834C>T

Variant names:

• chr17-74299827-C-T
• rs34159194
• NM_023036.6:c.834C>T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_023036.6(DNAI2):​c.834C>T​(p.Thr278Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.171 in 1,613,300 control chromosomes in the GnomAD database, including 25,959 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.13 (1593 hom., cov: 32)
  • Exomes 𝑓: 0.18 (24366 hom.)
• Consequence: DNAI2 NM_023036.6 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:11
• Conservation: PhyloP100: -6.05
• Publications: 7 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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.6).
• BP6: Variant 17-74299827-C-T is Benign according to our data. Variant chr17-74299827-C-T is described in ClinVar as Benign. ClinVar VariationId is 163167.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-6.05 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.185 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.834C>T	p.Thr278Thr	synonymous	Exon 7 of 14	NP_075462.3	Q9GZS0-1
	DNAI2	NM_001353167.2		c.834C>T	p.Thr278Thr	synonymous	Exon 7 of 15	NP_001340096.1
	DNAI2	NM_001172810.3		c.834C>T	p.Thr278Thr	synonymous	Exon 7 of 14	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.834C>T	p.Thr278Thr	synonymous	Exon 7 of 14	ENSP00000308312.6	Q9GZS0-1
	DNAI2	ENST00000579490.5	TSL:1	c.1005C>T	p.Thr335Thr	synonymous	Exon 6 of 13	ENSP00000464197.1	J3QRG2
	DNAI2	ENST00000446837.2	TSL:1	c.834C>T	p.Thr278Thr	synonymous	Exon 6 of 13	ENSP00000400252.2	Q9GZS0-1

Frequencies

GnomAD3 genomes AF: 0.127 AC: 19313 AN: 151972 Hom.: 1593 Cov.: 32

Gnomad AFR AF: 0.0376

Gnomad AMI AF: 0.129

Gnomad AMR AF: 0.0945

Gnomad ASJ AF: 0.135

Gnomad EAS AF: 0.00327

Gnomad SAS AF: 0.124

Gnomad FIN AF: 0.196

Gnomad MID AF: 0.0791

Gnomad NFE AF: 0.188

Gnomad OTH AF: 0.112

GnomAD2 exomes AF: 0.138 AC: 34550 AN: 250330 AF XY: 0.144

Gnomad AFR exome AF: 0.0351

Gnomad AMR exome AF: 0.0644

Gnomad ASJ exome AF: 0.125

Gnomad EAS exome AF: 0.00234

Gnomad FIN exome AF: 0.196

Gnomad NFE exome AF: 0.189

Gnomad OTH exome AF: 0.138

GnomAD4 exome AF: 0.176 AC: 256543 AN: 1461210 Hom.: 24366 Cov.: 35 AF XY: 0.175 AC XY: 127412 AN XY: 726880

African (AFR) AF: 0.0314 AC: 1051 AN: 33480

American (AMR) AF: 0.0668 AC: 2989 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.127 AC: 3318 AN: 26136

East Asian (EAS) AF: 0.00108 AC: 43 AN: 39700

South Asian (SAS) AF: 0.135 AC: 11615 AN: 86244

European-Finnish (FIN) AF: 0.197 AC: 10409 AN: 52844

Middle Eastern (MID) AF: 0.114 AC: 657 AN: 5768

European-Non Finnish (NFE) AF: 0.196 AC: 217669 AN: 1111936

Other (OTH) AF: 0.146 AC: 8792 AN: 60382

GnomAD4 genome AF: 0.127 AC: 19313 AN: 152090 Hom.: 1593 Cov.: 32 AF XY: 0.125 AC XY: 9294 AN XY: 74310

African (AFR) AF: 0.0374 AC: 1555 AN: 41532

American (AMR) AF: 0.0943 AC: 1441 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.135 AC: 469 AN: 3470

East Asian (EAS) AF: 0.00328 AC: 17 AN: 5184

South Asian (SAS) AF: 0.126 AC: 605 AN: 4810

European-Finnish (FIN) AF: 0.196 AC: 2065 AN: 10558

Middle Eastern (MID) AF: 0.0850 AC: 25 AN: 294

European-Non Finnish (NFE) AF: 0.188 AC: 12786 AN: 67944

Other (OTH) AF: 0.111 AC: 233 AN: 2104

Alfa AF: 0.155 Hom.: 1901

Bravo AF: 0.114

Asia WGS AF: 0.0560 AC: 196 AN: 3478

EpiCase AF: 0.174

EpiControl AF: 0.170

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not specified (3)
-	-	3	Primary ciliary dyskinesia (3)
-	-	3	Primary ciliary dyskinesia 9 (3)
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.60
CADD	Benign	0.18
DANN	Benign	0.66
PhyloP100		-6.1
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs34159194; hg19: chr17-72295966; COSMIC: COSV56758353;