dbSNP rs1544725: DNAH2:c.-255C>A (chr17-7718559-C-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_020877.5(DNAH2):c.-255C>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.153 in 152,240 control chromosomes in the GnomAD database, including 2,364 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 0.15 ( 2364 hom., cov: 32)

Exomes 𝑓: 0.041 ( 0 hom. )

Consequence

DNAH2
NM_020877.5 5_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.00600

Publications

2 publications found

Variant links:

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

DNAH2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.67).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.283 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNAH2	NM_020877.5 link	c.-255C>A		5_prime_UTR_variant	Exon 1 of 86	ENST00000572933.6	NP_065928.2	Q9P225-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DNAH2	ENST00000572933.6 link	c.-255C>A		5_prime_UTR_variant	Exon 1 of 86	2	NM_020877.5	ENSP00000458355.1		Q9P225-1
DNAH2	ENST00000570791.5 link	c.-15+728C>A		intron_variant	Intron 1 of 13	1		ENSP00000460245.1		Q9P225-3

Frequencies

GnomAD3 genomes

AF:

0.153

AC:

23196

AN:

151998

Hom.:

2361

Cov.:

show subpopulations

Gnomad AFR

AF:

0.288

Gnomad AMI

AF:

0.0921

Gnomad AMR

AF:

0.134

Gnomad ASJ

AF:

0.0792

Gnomad EAS

AF:

0.194

Gnomad SAS

AF:

0.175

Gnomad FIN

AF:

0.0520

Gnomad MID

AF:

0.117

Gnomad NFE

AF:

0.0912

Gnomad OTH

AF:

0.131

GnomAD4 exome

AF:

0.0410

AC:

AN:

122

Hom.:

Cov.:

AF XY:

0.0395

AC XY:

AN XY:

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.0364

AC:

AN:

110

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.167

AC:

AN:

Other (OTH)

AF:

0.00

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.585

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.153

AC:

23216

AN:

152118

Hom.:

2364

Cov.:

AF XY:

0.151

AC XY:

11198

AN XY:

74372

show subpopulations

African (AFR)

AF:

0.287

AC:

11909

AN:

41448

American (AMR)

AF:

0.133

AC:

2042

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.0792

AC:

275

AN:

3472

East Asian (EAS)

AF:

0.194

AC:

1001

AN:

5168

South Asian (SAS)

AF:

0.175

AC:

844

AN:

4822

European-Finnish (FIN)

AF:

0.0520

AC:

552

AN:

10612

Middle Eastern (MID)

AF:

0.116

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0912

AC:

6202

AN:

67982

Other (OTH)

AF:

0.129

AC:

273

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

955

1911

2866

3822

4777

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

242

484

726

968

1210

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.111

Hom.:

1599

Bravo

AF:

0.164

Asia WGS

AF:

0.178

AC:

619

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.67

CADD

Benign

9.1

(source)

DANN

Benign

0.89

PhyloP100

-0.0060

Mutation Taster

=299/1

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over