NM_020877.5:c.8972+9G>C

Variant names:

• chr17-7802026-G-C
• rs8073196
• NM_020877.5:c.8972+9G>C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_020877.5(DNAH2):​c.8972+9G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.268 in 1,613,706 control chromosomes in the GnomAD database, including 63,201 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.21 (4382 hom., cov: 32)
  • Exomes 𝑓: 0.27 (58819 hom.)
• Consequence: DNAH2 NM_020877.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -3.09
• Publications: 8 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 17-7802026-G-C is Benign according to our data. Variant chr17-7802026-G-C is described in ClinVar as Benign. ClinVar VariationId is 402711.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.301 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNAH2	NM_020877.5	c.8972+9G>C		intron_variant	Intron 58 of 85	ENST00000572933.6	NP_065928.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DNAH2	ENST00000572933.6	c.8972+9G>C		intron_variant	Intron 58 of 85	2	NM_020877.5	ENSP00000458355.1
DNAH2	ENST00000389173.6	c.8972+9G>C		intron_variant	Intron 57 of 84	2		ENSP00000373825.2

Frequencies

GnomAD3 genomes AF: 0.215 AC: 32653 AN: 152034 Hom.: 4384 Cov.: 32

Gnomad AFR AF: 0.0818

Gnomad AMI AF: 0.257

Gnomad AMR AF: 0.198

Gnomad ASJ AF: 0.290

Gnomad EAS AF: 0.00212

Gnomad SAS AF: 0.142

Gnomad FIN AF: 0.288

Gnomad MID AF: 0.291

Gnomad NFE AF: 0.304

Gnomad OTH AF: 0.227

GnomAD2 exomes AF: 0.224 AC: 56197 AN: 250980 AF XY: 0.229

Gnomad AFR exome AF: 0.0757

Gnomad AMR exome AF: 0.145

Gnomad ASJ exome AF: 0.289

Gnomad EAS exome AF: 0.000598

Gnomad FIN exome AF: 0.295

Gnomad NFE exome AF: 0.305

Gnomad OTH exome AF: 0.270

GnomAD4 exome AF: 0.273 AC: 399373 AN: 1461554 Hom.: 58819 Cov.: 38 AF XY: 0.271 AC XY: 197234 AN XY: 727074

African (AFR) AF: 0.0758 AC: 2538 AN: 33478

American (AMR) AF: 0.151 AC: 6750 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.296 AC: 7727 AN: 26134

East Asian (EAS) AF: 0.000453 AC: 18 AN: 39700

South Asian (SAS) AF: 0.148 AC: 12795 AN: 86252

European-Finnish (FIN) AF: 0.291 AC: 15470 AN: 53238

Middle Eastern (MID) AF: 0.300 AC: 1731 AN: 5764

European-Non Finnish (NFE) AF: 0.303 AC: 337065 AN: 1111886

Other (OTH) AF: 0.253 AC: 15279 AN: 60382

GnomAD4 genome AF: 0.215 AC: 32640 AN: 152152 Hom.: 4382 Cov.: 32 AF XY: 0.210 AC XY: 15617 AN XY: 74372

African (AFR) AF: 0.0815 AC: 3385 AN: 41532

American (AMR) AF: 0.197 AC: 3014 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.290 AC: 1008 AN: 3470

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

South Asian (SAS) AF: 0.143 AC: 688 AN: 4828

European-Finnish (FIN) AF: 0.288 AC: 3044 AN: 10566

Middle Eastern (MID) AF: 0.293 AC: 86 AN: 294

European-Non Finnish (NFE) AF: 0.304 AC: 20696 AN: 67976

Other (OTH) AF: 0.224 AC: 474 AN: 2112

Alfa AF: 0.178 Hom.: 530

Bravo AF: 0.202

Asia WGS AF: 0.0600 AC: 209 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Mar 29, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency -

DNAH2-related disorder Benign:1

Oct 21, 2019

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

not provided Benign:1

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.010
DANN	Benign	0.64
PhyloP100		-3.1
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs8073196; hg19: chr17-7705344;