rs6501706

Variant names:

• chr17-74285228-A-G
• rs6501706
• NM_023036.6:c.345+27A>G

Your query was ambiguous. Multiple possible variants found:

• chr17-74285228-A-G
• chr17-74285228-A-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.345+27A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.992 in 1,611,748 control chromosomes in the GnomAD database, including 793,740 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.96 (70501 hom., cov: 32)
  • Exomes 𝑓: 1.0 (723239 hom.)
• Consequence: DNAI2 NM_023036.6 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -0.346
• Publications: 9 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

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 17-74285228-A-G is Benign according to our data. Variant chr17-74285228-A-G is described in ClinVar as Benign. ClinVar VariationId is 261648.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.993 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNAI2	NM_023036.6	c.345+27A>G		intron_variant	Intron 3 of 13	ENST00000311014.11	NP_075462.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DNAI2	ENST00000311014.11	c.345+27A>G		intron_variant	Intron 3 of 13	1	NM_023036.6	ENSP00000308312.6

Frequencies

GnomAD3 genomes AF: 0.960 AC: 146129 AN: 152162 Hom.: 70464 Cov.: 32

Gnomad AFR AF: 0.864

Gnomad AMI AF: 1.00

Gnomad AMR AF: 0.982

Gnomad ASJ AF: 0.996

Gnomad EAS AF: 1.00

Gnomad SAS AF: 1.00

Gnomad FIN AF: 1.00

Gnomad MID AF: 0.978

Gnomad NFE AF: 0.999

Gnomad OTH AF: 0.974

GnomAD2 exomes AF: 0.990 AC: 243934 AN: 246512 AF XY: 0.992

Gnomad AFR exome AF: 0.867

Gnomad AMR exome AF: 0.991

Gnomad ASJ exome AF: 0.996

Gnomad EAS exome AF: 1.00

Gnomad FIN exome AF: 1.00

Gnomad NFE exome AF: 0.999

Gnomad OTH exome AF: 0.993

GnomAD4 exome AF: 0.995 AC: 1452612 AN: 1459468 Hom.: 723239 Cov.: 43 AF XY: 0.996 AC XY: 722736 AN XY: 725804

African (AFR) AF: 0.856 AC: 28627 AN: 33428

American (AMR) AF: 0.990 AC: 43818 AN: 44244

Ashkenazi Jewish (ASJ) AF: 0.996 AC: 25965 AN: 26072

East Asian (EAS) AF: 1.00 AC: 39637 AN: 39640

South Asian (SAS) AF: 1.00 AC: 85734 AN: 85774

European-Finnish (FIN) AF: 1.00 AC: 53229 AN: 53230

Middle Eastern (MID) AF: 0.983 AC: 5668 AN: 5766

European-Non Finnish (NFE) AF: 0.999 AC: 1110278 AN: 1110994

Other (OTH) AF: 0.989 AC: 59656 AN: 60320

GnomAD4 genome AF: 0.960 AC: 146218 AN: 152280 Hom.: 70501 Cov.: 32 AF XY: 0.962 AC XY: 71599 AN XY: 74440

African (AFR) AF: 0.864 AC: 35895 AN: 41552

American (AMR) AF: 0.982 AC: 15026 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.996 AC: 3459 AN: 3472

East Asian (EAS) AF: 1.00 AC: 5174 AN: 5174

South Asian (SAS) AF: 1.00 AC: 4818 AN: 4820

European-Finnish (FIN) AF: 1.00 AC: 10614 AN: 10614

Middle Eastern (MID) AF: 0.980 AC: 288 AN: 294

European-Non Finnish (NFE) AF: 0.999 AC: 67971 AN: 68026

Other (OTH) AF: 0.974 AC: 2061 AN: 2116

Alfa AF: 0.981 Hom.: 13485

Bravo AF: 0.954

Asia WGS AF: 0.989 AC: 3440 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Apr 10, 2019

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 v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.17
DANN	Benign	0.35
PhyloP100		-0.35
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: rs6501706; hg19: chr17-72281367;