chr17-74310131-C-G

Variant names:

• chr17-74310131-C-G
• rs61736879
• NM_023036.6:c.1462C>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_023036.6(DNAI2):​c.1462C>G​(p.Leu488Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. L488F) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: DNAI2 NM_023036.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.61
• Publications: 4 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

LOC105371891 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.103779286).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNAI2	NM_023036.6	c.1462C>G	p.Leu488Val	missense_variant	Exon 11 of 14	ENST00000311014.11	NP_075462.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DNAI2	ENST00000311014.11	c.1462C>G	p.Leu488Val	missense_variant	Exon 11 of 14	1	NM_023036.6	ENSP00000308312.6

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 36

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 2

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.095
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.39
CADD	Benign	16
DANN	Benign	0.55
DEOGEN2	Benign	0.0098	.;T;T;T
Eigen	Benign	-0.65
Eigen_PC	Benign	-0.56
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Benign	0.81	T;.;T;T
M_CAP	Benign	0.0091	T
MetaRNN	Benign	0.10	T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.1	.;M;M;.
PhyloP100		1.6
PrimateAI	Uncertain	0.49	T
PROVEAN	Benign	-2.0	.;N;N;.
REVEL	Benign	0.25
Sift	Benign	0.61	.;T;T;.
Sift4G	Benign	0.61	T;T;T;T
Polyphen		0.013	.;B;B;.
Vest4		0.20
MutPred		0.32		.;Loss of sheet (P = 0.0817);Loss of sheet (P = 0.0817);.;
MVP		0.29
MPC		0.24
ClinPred		0.085	T
GERP RS		4.3
Varity_R		0.11
gMVP		0.37
Mutation Taster		=81/19	polymorphism

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: rs61736879; hg19: chr17-72306270;