NM_020877.5:c.5265C>G

Variant names:

• chr17-7778094-C-G
• rs7359662
• NM_020877.5:c.5265C>G

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_020877.5(DNAH2):​c.5265C>G​(p.Val1755Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.908 in 1,613,820 control chromosomes in the GnomAD database, including 672,803 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.81 (52302 hom., cov: 31)
  • Exomes 𝑓: 0.92 (620501 hom.)
• Consequence: DNAH2 NM_020877.5 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.0290
• Publications: 16 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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.56).
• BP6: Variant 17-7778094-C-G is Benign according to our data. Variant chr17-7778094-C-G is described in ClinVar as Benign. ClinVar VariationId is 402709.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.029 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.934 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.5265C>G	p.Val1755Val	synonymous	Exon 34 of 86	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.5265C>G	p.Val1755Val	synonymous	Exon 34 of 86	ENSP00000458355.1	Q9P225-1
	DNAH2	ENST00000389173.6	TSL:2	c.5265C>G	p.Val1755Val	synonymous	Exon 33 of 85	ENSP00000373825.2	Q9P225-1
	DNAH2	ENST00000574518.1	TSL:2	n.*1641C>G		non_coding_transcript_exon	Exon 15 of 22	ENSP00000461273.1	I3L4H9

Frequencies

GnomAD3 genomes AF: 0.806 AC: 122591 AN: 152006 Hom.: 52282 Cov.: 31

Gnomad AFR AF: 0.505

Gnomad AMI AF: 0.922

Gnomad AMR AF: 0.861

Gnomad ASJ AF: 0.905

Gnomad EAS AF: 0.807

Gnomad SAS AF: 0.872

Gnomad FIN AF: 0.971

Gnomad MID AF: 0.807

Gnomad NFE AF: 0.940

Gnomad OTH AF: 0.820

GnomAD2 exomes AF: 0.881 AC: 221642 AN: 251442 AF XY: 0.888

Gnomad AFR exome AF: 0.500

Gnomad AMR exome AF: 0.871

Gnomad ASJ exome AF: 0.907

Gnomad EAS exome AF: 0.801

Gnomad FIN exome AF: 0.967

Gnomad NFE exome AF: 0.937

Gnomad OTH exome AF: 0.903

GnomAD4 exome AF: 0.918 AC: 1342151 AN: 1461696 Hom.: 620501 Cov.: 49 AF XY: 0.918 AC XY: 667388 AN XY: 727178

African (AFR) AF: 0.492 AC: 16459 AN: 33472

American (AMR) AF: 0.872 AC: 39014 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.909 AC: 23757 AN: 26136

East Asian (EAS) AF: 0.798 AC: 31673 AN: 39698

South Asian (SAS) AF: 0.865 AC: 74617 AN: 86246

European-Finnish (FIN) AF: 0.967 AC: 51637 AN: 53418

Middle Eastern (MID) AF: 0.822 AC: 4742 AN: 5768

European-Non Finnish (NFE) AF: 0.941 AC: 1046376 AN: 1111840

Other (OTH) AF: 0.892 AC: 53876 AN: 60394

GnomAD4 genome AF: 0.806 AC: 122657 AN: 152124 Hom.: 52302 Cov.: 31 AF XY: 0.811 AC XY: 60306 AN XY: 74374

African (AFR) AF: 0.506 AC: 20951 AN: 41444

American (AMR) AF: 0.861 AC: 13165 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.905 AC: 3141 AN: 3472

East Asian (EAS) AF: 0.806 AC: 4172 AN: 5174

South Asian (SAS) AF: 0.871 AC: 4198 AN: 4818

European-Finnish (FIN) AF: 0.971 AC: 10301 AN: 10606

Middle Eastern (MID) AF: 0.803 AC: 236 AN: 294

European-Non Finnish (NFE) AF: 0.940 AC: 63917 AN: 68012

Other (OTH) AF: 0.822 AC: 1735 AN: 2110

Alfa AF: 0.898 Hom.: 20250

Bravo AF: 0.785

Asia WGS AF: 0.849 AC: 2952 AN: 3478

EpiCase AF: 0.935

EpiControl AF: 0.929

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	-0.56
CADD	Benign	1.9
DANN	Benign	0.61
PhyloP100		0.029
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs7359662; hg19: chr17-7681412; COSMIC: COSV101209243;