rs3744258

Positions:

• chr17-7720076-A-G
• chr17-7720076-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_020877.5(DNAH2):​c.166+176A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.307 in 151,830 control chromosomes in the GnomAD database, including 7,564 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.31 (7564 hom., cov: 31)
• Consequence: DNAH2 NM_020877.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.164

Genes affected

DNAH2 (HGNC:2948): (dynein axonemal heavy chain 2) Dyneins are microtubule-associated motor protein complexes composed of several heavy, light, and intermediate chains. The axonemal dyneins, found in cilia and flagella, are components of the outer and inner dynein arms attached to the peripheral microtubule doublets. DNAH2 is an axonemal inner arm dynein heavy chain (Chapelin et al., 1997 [PubMed 9256245]).[supplied by OMIM, Mar 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.455 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DNAH2	NM_020877.5	c.166+176A>G		intron_variant		ENST00000572933.6	NP_065928.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DNAH2	ENST00000572933.6	c.166+176A>G		intron_variant		2	NM_020877.5	ENSP00000458355.1
DNAH2	ENST00000570791.5	c.166+176A>G		intron_variant		1		ENSP00000460245.1
DNAH2	ENST00000389173.6	c.166+176A>G		intron_variant		2		ENSP00000373825.2

Frequencies

GnomAD3 genomes AF: 0.307 AC: 46576 AN: 151712 Hom.: 7567 Cov.: 31

Gnomad AFR AF: 0.207

Gnomad AMI AF: 0.319

Gnomad AMR AF: 0.311

Gnomad ASJ AF: 0.371

Gnomad EAS AF: 0.472

Gnomad SAS AF: 0.280

Gnomad FIN AF: 0.320

Gnomad MID AF: 0.377

Gnomad NFE AF: 0.350

Gnomad OTH AF: 0.332

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.307 AC: 46579 AN: 151830 Hom.: 7564 Cov.: 31 AF XY: 0.306 AC XY: 22696 AN XY: 74186

Gnomad4 AFR AF: 0.207

Gnomad4 AMR AF: 0.310

Gnomad4 ASJ AF: 0.371

Gnomad4 EAS AF: 0.471

Gnomad4 SAS AF: 0.279

Gnomad4 FIN AF: 0.320

Gnomad4 NFE AF: 0.350

Gnomad4 OTH AF: 0.330

Alfa AF: 0.342 Hom.: 11994

Bravo AF: 0.304

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	4.3
DANN	Benign	0.46

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

Other links and lift over

dbSNP: rs3744258; hg19: chr17-7623394;