rs872346

Variant names:

• chr17-7817712-G-A
• rs872346
• NM_020877.5:c.10169+3G>A

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.10169+3G>A variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.344 in 1,613,956 control chromosomes in the GnomAD database, including 103,051 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.28 (6908 hom., cov: 31)
  • Exomes 𝑓: 0.35 (96143 hom.)
• Consequence: DNAH2 NM_020877.5 splice_region, intron
• Scores: Splicing: ADA: 0.00002793
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -1.05
• Publications: 17 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=-0.91).
• BP6: Variant 17-7817712-G-A is Benign according to our data. Variant chr17-7817712-G-A is described in ClinVar as Benign. ClinVar VariationId is 402712.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.387 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAH2	NM_020877.5	MANE Select	c.10169+3G>A		splice_region intron	N/A	NP_065928.2	Q9P225-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAH2	ENST00000572933.6	TSL:2 MANE Select	c.10169+3G>A		splice_region intron	N/A	ENSP00000458355.1	Q9P225-1
	DNAH2	ENST00000389173.6	TSL:2	c.10169+3G>A		splice_region intron	N/A	ENSP00000373825.2	Q9P225-1
	DNAH2	ENST00000575105.1	TSL:5	c.1016+3G>A		splice_region intron	N/A	ENSP00000461726.1	I3L520

Frequencies

GnomAD3 genomes AF: 0.277 AC: 42068 AN: 151970 Hom.: 6902 Cov.: 31

Gnomad AFR AF: 0.126

Gnomad AMI AF: 0.378

Gnomad AMR AF: 0.256

Gnomad ASJ AF: 0.356

Gnomad EAS AF: 0.0637

Gnomad SAS AF: 0.159

Gnomad FIN AF: 0.280

Gnomad MID AF: 0.411

Gnomad NFE AF: 0.391

Gnomad OTH AF: 0.311

GnomAD2 exomes AF: 0.280 AC: 70247 AN: 251192 AF XY: 0.286

Gnomad AFR exome AF: 0.116

Gnomad AMR exome AF: 0.187

Gnomad ASJ exome AF: 0.360

Gnomad EAS exome AF: 0.0626

Gnomad FIN exome AF: 0.286

Gnomad NFE exome AF: 0.387

Gnomad OTH exome AF: 0.326

GnomAD4 exome AF: 0.351 AC: 512761 AN: 1461866 Hom.: 96143 Cov.: 86 AF XY: 0.347 AC XY: 252292 AN XY: 727228

African (AFR) AF: 0.111 AC: 3715 AN: 33480

American (AMR) AF: 0.193 AC: 8632 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.362 AC: 9469 AN: 26136

East Asian (EAS) AF: 0.0681 AC: 2702 AN: 39700

South Asian (SAS) AF: 0.163 AC: 14034 AN: 86258

European-Finnish (FIN) AF: 0.285 AC: 15211 AN: 53410

Middle Eastern (MID) AF: 0.370 AC: 2132 AN: 5768

European-Non Finnish (NFE) AF: 0.393 AC: 436845 AN: 1111994

Other (OTH) AF: 0.331 AC: 20021 AN: 60396

GnomAD4 genome AF: 0.277 AC: 42107 AN: 152090 Hom.: 6908 Cov.: 31 AF XY: 0.268 AC XY: 19939 AN XY: 74346

African (AFR) AF: 0.126 AC: 5243 AN: 41530

American (AMR) AF: 0.256 AC: 3910 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.356 AC: 1237 AN: 3472

East Asian (EAS) AF: 0.0639 AC: 330 AN: 5166

South Asian (SAS) AF: 0.160 AC: 769 AN: 4820

European-Finnish (FIN) AF: 0.280 AC: 2957 AN: 10570

Middle Eastern (MID) AF: 0.412 AC: 121 AN: 294

European-Non Finnish (NFE) AF: 0.391 AC: 26543 AN: 67942

Other (OTH) AF: 0.310 AC: 654 AN: 2112

Alfa AF: 0.358 Hom.: 20865

Bravo AF: 0.269

Asia WGS AF: 0.124 AC: 430 AN: 3478

EpiCase AF: 0.409

EpiControl AF: 0.401

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	DNAH2-related disorder (1)
-	-	1	not provided (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.082
DANN	Benign	0.57
PhyloP100		-1.0
Mutation Taster		=92/8	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000028
dbscSNV1_RF	Benign	0.036
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: rs872346; hg19: chr17-7721030; COSMIC: COSV66719233;