chr17-74312271-C-T

Variant names:

• chr17-74312271-C-T
• rs4239009
• NM_023036.6:c.1722+41C>T

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+41C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.893 in 528,754 control chromosomes in the GnomAD database, including 214,228 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.85 (55673 hom., cov: 26)
  • Exomes 𝑓: 0.91 (158555 hom.)
• Consequence: DNAI2 NM_023036.6 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -2.38
• Publications: 8 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: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BP6: Variant 17-74312271-C-T is Benign according to our data. Variant chr17-74312271-C-T is described in ClinVar as Benign. ClinVar VariationId is 261646.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.926 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAI2	NM_023036.6	MANE Select	c.1722+41C>T		intron	N/A	NP_075462.3
	DNAI2	NM_001353167.2		c.1722+41C>T		intron	N/A	NP_001340096.1
	DNAI2	NM_001172810.3		c.1686+41C>T		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+41C>T		intron	N/A	ENSP00000308312.6
	DNAI2	ENST00000579490.5	TSL:1	c.1893+41C>T		intron	N/A	ENSP00000464197.1
	DNAI2	ENST00000446837.2	TSL:1	c.1722+41C>T		intron	N/A	ENSP00000400252.2

Frequencies

GnomAD3 genomes AF: 0.854 AC: 127903 AN: 149728 Hom.: 55657 Cov.: 26

Gnomad AFR AF: 0.666

Gnomad AMI AF: 0.942

Gnomad AMR AF: 0.912

Gnomad ASJ AF: 0.905

Gnomad EAS AF: 0.889

Gnomad SAS AF: 0.931

Gnomad FIN AF: 0.924

Gnomad MID AF: 0.867

Gnomad NFE AF: 0.933

Gnomad OTH AF: 0.852

GnomAD2 exomes AF: 0.917 AC: 130211 AN: 141956 AF XY: 0.920

Gnomad AFR exome AF: 0.654

Gnomad AMR exome AF: 0.951

Gnomad ASJ exome AF: 0.899

Gnomad EAS exome AF: 0.897

Gnomad FIN exome AF: 0.929

Gnomad NFE exome AF: 0.936

Gnomad OTH exome AF: 0.921

GnomAD4 exome AF: 0.908 AC: 344005 AN: 378910 Hom.: 158555 Cov.: 3 AF XY: 0.912 AC XY: 187738 AN XY: 205936

African (AFR) AF: 0.560 AC: 7186 AN: 12834

American (AMR) AF: 0.947 AC: 26358 AN: 27822

Ashkenazi Jewish (ASJ) AF: 0.894 AC: 11998 AN: 13422

East Asian (EAS) AF: 0.882 AC: 15644 AN: 17738

South Asian (SAS) AF: 0.929 AC: 55833 AN: 60100

European-Finnish (FIN) AF: 0.926 AC: 29608 AN: 31976

Middle Eastern (MID) AF: 0.871 AC: 1670 AN: 1918

European-Non Finnish (NFE) AF: 0.921 AC: 179220 AN: 194496

Other (OTH) AF: 0.886 AC: 16488 AN: 18604

GnomAD4 genome AF: 0.854 AC: 127963 AN: 149844 Hom.: 55673 Cov.: 26 AF XY: 0.857 AC XY: 62503 AN XY: 72952

African (AFR) AF: 0.665 AC: 27096 AN: 40734

American (AMR) AF: 0.913 AC: 13639 AN: 14946

Ashkenazi Jewish (ASJ) AF: 0.905 AC: 3134 AN: 3464

East Asian (EAS) AF: 0.889 AC: 4384 AN: 4934

South Asian (SAS) AF: 0.931 AC: 4426 AN: 4752

European-Finnish (FIN) AF: 0.924 AC: 9148 AN: 9898

Middle Eastern (MID) AF: 0.864 AC: 254 AN: 294

European-Non Finnish (NFE) AF: 0.932 AC: 63241 AN: 67820

Other (OTH) AF: 0.853 AC: 1784 AN: 2092

Alfa AF: 0.890 Hom.: 14532

Bravo AF: 0.844

Asia WGS AF: 0.896 AC: 3116 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Nov 11, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

not specified Benign:1

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Primary ciliary dyskinesia 9 Benign:1

Jul 10, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.0020
DANN	Benign	0.70
PhyloP100		-2.4
Mutation Taster		=100/0	polymorphism (auto)

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: rs4239009; hg19: chr17-72308410;