Variant 17-74312152-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_023036.6(DNAI2):c.1644C>A(p.Ala548Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0321 in 1,612,522 control chromosomes in the GnomAD database, including 954 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.039 ( 126 hom., cov: 33)

Exomes 𝑓: 0.031 ( 828 hom. )

Consequence

DNAI2
NM_023036.6 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:9

Conservation

PhyloP100: -2.68

Variant links:

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 links:

DNAI2 (HGNC:):

DNAI2 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.43).

BP6

Variant 17-74312152-C-A is Benign according to our data. Variant chr17-74312152-C-A is described in ClinVar as [Benign]. Clinvar id is 163170.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-74312152-C-A is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-2.68 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0549 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DNAI2	NM_023036.6 linkuse as main transcript	c.1644C>A	p.Ala548Ala	synonymous_variant	12/14	ENST00000311014.11	NP_075462.3	Q9GZS0-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DNAI2	ENST00000311014.11 linkuse as main transcript	c.1644C>A	p.Ala548Ala	synonymous_variant	12/14	1	NM_023036.6	ENSP00000308312.6		Q9GZS0-1

Frequencies

GnomAD3 genomes

AF:

0.0389

AC:

5891

AN:

151510

Hom.:

125

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0567

Gnomad AMI

AF:

0.0176

Gnomad AMR

AF:

0.0320

Gnomad ASJ

AF:

0.0346

Gnomad EAS

AF:

0.000195

Gnomad SAS

AF:

0.0332

Gnomad FIN

AF:

0.0385

Gnomad MID

AF:

0.0506

Gnomad NFE

AF:

0.0332

Gnomad OTH

AF:

0.0470

GnomAD3 exomes

AF:

0.0312

AC:

7785

AN:

249636

Hom.:

156

AF XY:

0.0316

AC XY:

4268

AN XY:

135218

show subpopulations

Gnomad AFR exome

AF:

0.0574

Gnomad AMR exome

AF:

0.0176

Gnomad ASJ exome

AF:

0.0394

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0347

Gnomad FIN exome

AF:

0.0365

Gnomad NFE exome

AF:

0.0339

Gnomad OTH exome

AF:

0.0325

GnomAD4 exome

AF:

0.0314

AC:

45845

AN:

1460894

Hom.:

828

Cov.:

AF XY:

0.0313

AC XY:

22780

AN XY:

726706

show subpopulations

Gnomad4 AFR exome

AF:

0.0582

Gnomad4 AMR exome

AF:

0.0198

Gnomad4 ASJ exome

AF:

0.0383

Gnomad4 EAS exome

AF:

0.0000756

Gnomad4 SAS exome

AF:

0.0357

Gnomad4 FIN exome

AF:

0.0355

Gnomad4 NFE exome

AF:

0.0312

Gnomad4 OTH exome

AF:

0.0346

GnomAD4 genome

AF:

0.0389

AC:

5902

AN:

151628

Hom.:

126

Cov.:

AF XY:

0.0378

AC XY:

2800

AN XY:

74092

show subpopulations

Gnomad4 AFR

AF:

0.0568

Gnomad4 AMR

AF:

0.0320

Gnomad4 ASJ

AF:

0.0346

Gnomad4 EAS

AF:

0.000196

Gnomad4 SAS

AF:

0.0328

Gnomad4 FIN

AF:

0.0385

Gnomad4 NFE

AF:

0.0332

Gnomad4 OTH

AF:

0.0465

Alfa

AF:

0.0238

Hom.:

Bravo

AF:

0.0391

EpiCase

AF:

0.0361

EpiControl

AF:

0.0355

ClinVar

Significance: Benign

Submissions summary: Benign:9

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Primary ciliary dyskinesia

Benign:3

Benign, no assertion criteria provided	clinical testing	Natera, Inc.	Sep 16, 2020	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -
Benign, criteria provided, single submitter	clinical testing	Ambry Genetics	Dec 24, 2014	This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

not specified

Benign:2

Benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	Feb 21, 2013	Ala548Ala in exon 12 of DNAI2: This variant is not expected to have clinical sig nificance because it does not alter an amino acid residue and is not located wit hin the splice consensus sequence. It has been identified in 5.7% (252/4406) of African American chromosomes from a broad population by the NHLBI Exome Sequenci ng Project (http://evs.gs.washington.edu/EVS; dbSNP rs9908476). -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -

Primary ciliary dyskinesia 9

Benign:2

Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 13, 2018	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -
Benign, criteria provided, single submitter	clinical testing	Counsyl	Mar 06, 2017	- -

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Feb 21, 2019	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.43

CADD

Benign

0.059

DANN

Benign

0.78

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over