chr17-7720076-A-G

Variant names:

• chr17-7720076-A-G
• rs3744258
• NM_020877.5:c.166+176A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 12 publications found

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]

DNAH2 Gene-Disease associations (from GenCC):

• spermatogenic failure 45

  Inheritance: AR Classification: MODERATE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020877.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAH2	NM_020877.5	MANE Select	c.166+176A>G		intron	N/A	NP_065928.2
	DNAH2	NM_001303270.2		c.166+176A>G		intron	N/A	NP_001290199.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAH2	ENST00000572933.6	TSL:2 MANE Select	c.166+176A>G		intron	N/A	ENSP00000458355.1
	DNAH2	ENST00000570791.5	TSL:1	c.166+176A>G		intron	N/A	ENSP00000460245.1
	DNAH2	ENST00000389173.6	TSL:2	c.166+176A>G		intron	N/A	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

African (AFR) AF: 0.207 AC: 8575 AN: 41406

American (AMR) AF: 0.310 AC: 4734 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.371 AC: 1284 AN: 3462

East Asian (EAS) AF: 0.471 AC: 2428 AN: 5156

South Asian (SAS) AF: 0.279 AC: 1341 AN: 4812

European-Finnish (FIN) AF: 0.320 AC: 3371 AN: 10518

Middle Eastern (MID) AF: 0.384 AC: 113 AN: 294

European-Non Finnish (NFE) AF: 0.350 AC: 23747 AN: 67900

Other (OTH) AF: 0.330 AC: 696 AN: 2108

Alfa AF: 0.328 Hom.: 16192

Bravo AF: 0.304

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	4.3
DANN	Benign	0.46
PhyloP100		-0.16
PromoterAI		0.0082	Neutral
Mutation Taster		=99/1	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: rs3744258; hg19: chr17-7623394;