17-74281550-G-A

Variant names:

• chr17-74281550-G-A
• rs62065702
• ENST00000579490.5:c.-97G>A

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.-11-257G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.126 in 585,530 control chromosomes in the GnomAD database, including 5,367 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.12 (1171 hom., cov: 31)
  • Exomes 𝑓: 0.13 (4196 hom.)
• Consequence: DNAI2 NM_023036.6 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.365
• 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: 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=-0.93).
• BP6: Variant 17-74281550-G-A is Benign according to our data. Variant chr17-74281550-G-A is described in ClinVar as [Benign]. Clinvar id is 1249367.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.149 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNAI2	NM_023036.6	c.-11-257G>A		intron_variant	Intron 1 of 13	ENST00000311014.11	NP_075462.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DNAI2	ENST00000311014.11	c.-11-257G>A		intron_variant	Intron 1 of 13	1	NM_023036.6	ENSP00000308312.6

Frequencies

GnomAD3 genomes AF: 0.116 AC: 17614 AN: 152010 Hom.: 1172 Cov.: 31

Gnomad AFR AF: 0.0749

Gnomad AMI AF: 0.117

Gnomad AMR AF: 0.0742

Gnomad ASJ AF: 0.0956

Gnomad EAS AF: 0.00212

Gnomad SAS AF: 0.116

Gnomad FIN AF: 0.172

Gnomad MID AF: 0.0665

Gnomad NFE AF: 0.152

Gnomad OTH AF: 0.0964

GnomAD4 exome AF: 0.129 AC: 55972 AN: 433402 Hom.: 4196 Cov.: 3 AF XY: 0.130 AC XY: 29307 AN XY: 226244

African (AFR) AF: 0.0734 AC: 899 AN: 12252

American (AMR) AF: 0.0607 AC: 1085 AN: 17882

Ashkenazi Jewish (ASJ) AF: 0.0912 AC: 1231 AN: 13504

East Asian (EAS) AF: 0.000683 AC: 21 AN: 30742

South Asian (SAS) AF: 0.125 AC: 5138 AN: 40984

European-Finnish (FIN) AF: 0.168 AC: 4894 AN: 29096

Middle Eastern (MID) AF: 0.0995 AC: 190 AN: 1910

European-Non Finnish (NFE) AF: 0.151 AC: 39603 AN: 261578

Other (OTH) AF: 0.114 AC: 2911 AN: 25454

GnomAD4 genome AF: 0.116 AC: 17623 AN: 152128 Hom.: 1171 Cov.: 31 AF XY: 0.115 AC XY: 8518 AN XY: 74350

African (AFR) AF: 0.0751 AC: 3116 AN: 41518

American (AMR) AF: 0.0740 AC: 1131 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.0956 AC: 332 AN: 3472

East Asian (EAS) AF: 0.00212 AC: 11 AN: 5184

South Asian (SAS) AF: 0.116 AC: 559 AN: 4808

European-Finnish (FIN) AF: 0.172 AC: 1821 AN: 10562

Middle Eastern (MID) AF: 0.0680 AC: 20 AN: 294

European-Non Finnish (NFE) AF: 0.152 AC: 10325 AN: 67996

Other (OTH) AF: 0.0954 AC: 201 AN: 2108

Alfa AF: 0.0698 Hom.: 85

Bravo AF: 0.106

Asia WGS AF: 0.0550 AC: 193 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

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

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Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	2.5
DANN	Benign	0.42
PhyloP100		0.36
PromoterAI		-0.0017	Neutral
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: rs62065702; hg19: chr17-72277689;