Genetic Variant NM_020877.5:c.411G>C (chr17-7733098-G-C) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_020877.5(DNAH2):c.411G>C(p.Gln137His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,822 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

DNAH2
NM_020877.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.15

Publications

6 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:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.18533722).

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.411G>C	p.Gln137His	missense	Exon 5 of 86	NP_065928.2	Q9P225-1
	DNAH2	NM_001303270.2		c.411G>C	p.Gln137His	missense	Exon 5 of 14	NP_001290199.1	Q9P225-3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
DNAH2	ENST00000572933.6	TSL:2 MANE Select	c.411G>C	p.Gln137His	missense	Exon 5 of 86	ENSP00000458355.1	Q9P225-1
DNAH2	ENST00000570791.5	TSL:1	c.411G>C	p.Gln137His	missense	Exon 5 of 14	ENSP00000460245.1	Q9P225-3
DNAH2	ENST00000389173.6	TSL:2	c.411G>C	p.Gln137His	missense	Exon 4 of 85	ENSP00000373825.2	Q9P225-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1461822

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

727216

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33476

American (AMR)

AF:

0.00

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26134

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.00

AC:

AN:

86252

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53416

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5730

European-Non Finnish (NFE)

AF:

0.00000180

AC:

AN:

1112004

Other (OTH)

AF:

0.00

AC:

AN:

60386

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.450

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

Cov.:

Alfa

AF:

0.00

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.46

BayesDel_addAF

Benign

-0.11

BayesDel_noAF

Benign

-0.39

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.047

Eigen

Benign

-0.10

Eigen_PC

Benign

0.017

FATHMM_MKL

Uncertain

0.92

LIST_S2

Benign

0.74

M_CAP

Benign

0.013

MetaRNN

Benign

0.19

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.0

PhyloP100

2.2

PrimateAI

Benign

0.44

PROVEAN

Benign

-2.1

REVEL

Benign

0.14

Sift

Uncertain

0.0050

Sift4G

Uncertain

0.0020

Polyphen

0.037

Vest4

0.36

MutPred

0.53

Gain of sheet (P = 0.0827)

MVP

0.43

MPC

0.18

ClinPred

0.45

GERP RS

4.2

Varity_R

0.15

gMVP

0.56

Mutation Taster

=59/41

polymorphism

(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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over