rs839721

Positions:

• chr17-7736431-G-A

Variant summary

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

The NM_020877.5(DNAH2):​c.979-636G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.577 in 151,964 control chromosomes in the GnomAD database, including 25,416 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 0.58 (25416 hom., cov: 32)
• Consequence: DNAH2 NM_020877.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.405

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=-0.91).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.732 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DNAH2	NM_020877.5	c.979-636G>A		intron_variant		ENST00000572933.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DNAH2	ENST00000572933.6	c.979-636G>A		intron_variant		2	NM_020877.5	P1
DNAH2	ENST00000570791.5	c.979-636G>A		intron_variant		1
DNAH2	ENST00000389173.6	c.979-636G>A		intron_variant		2		P1

Frequencies

GnomAD3 genomes AF: 0.577 AC: 87575 AN: 151846 Hom.: 25408 Cov.: 32

Gnomad AFR AF: 0.572

Gnomad AMI AF: 0.585

Gnomad AMR AF: 0.570

Gnomad ASJ AF: 0.589

Gnomad EAS AF: 0.721

Gnomad SAS AF: 0.754

Gnomad FIN AF: 0.563

Gnomad MID AF: 0.554

Gnomad NFE AF: 0.559

Gnomad OTH AF: 0.572

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

GnomAD4 genome AF: 0.577 AC: 87620 AN: 151964 Hom.: 25416 Cov.: 32 AF XY: 0.580 AC XY: 43093 AN XY: 74302

Gnomad4 AFR AF: 0.571

Gnomad4 AMR AF: 0.570

Gnomad4 ASJ AF: 0.589

Gnomad4 EAS AF: 0.721

Gnomad4 SAS AF: 0.752

Gnomad4 FIN AF: 0.563

Gnomad4 NFE AF: 0.559

Gnomad4 OTH AF: 0.576

Alfa AF: 0.568 Hom.: 51274

Bravo AF: 0.572

Asia WGS AF: 0.730 AC: 2539 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.1
DANN	Benign	0.51

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: rs839721; hg19: chr17-7639749;