dbSNP rs7213894: DNAH2:p.Thr3600Asn (chr17-7819047-C-A) – 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.10799C>A(p.Thr3600Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000138 in 1,453,708 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 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 variant affecting the same amino acid position, but resulting in a different missense (i.e. T3600I) has been classified as Benign.

Frequency

Genomes: not found (cov: 29)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

DNAH2
NM_020877.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.93

Publications

0 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: 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=0.12027371).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNAH2	NM_020877.5 link	c.10799C>A	p.Thr3600Asn	missense_variant	Exon 71 of 86	ENST00000572933.6	NP_065928.2	Q9P225-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
DNAH2	ENST00000572933.6 link	c.10799C>A	p.Thr3600Asn	missense_variant	Exon 71 of 86	2	NM_020877.5	ENSP00000458355.1	Q9P225-1
DNAH2	ENST00000389173.6 link	c.10799C>A	p.Thr3600Asn	missense_variant	Exon 70 of 85	2		ENSP00000373825.2	Q9P225-1
DNAH2	ENST00000575105.1 link	c.1646C>A	p.Thr549Asn	missense_variant	Exon 12 of 23	5		ENSP00000461726.1	I3L520

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000138

AC:

AN:

1453708

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

723184

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33426

American (AMR)

AF:

0.00

AC:

AN:

44420

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26094

East Asian (EAS)

AF:

0.00

AC:

AN:

39586

South Asian (SAS)

AF:

0.00

AC:

AN:

86056

European-Finnish (FIN)

AF:

0.00

AC:

AN:

47512

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5498

European-Non Finnish (NFE)

AF:

0.00000180

AC:

AN:

1110882

Other (OTH)

AF:

0.00

AC:

AN:

60234

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.550

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.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.53

BayesDel_addAF

Benign

-0.13

BayesDel_noAF

Benign

-0.42

CADD

Benign

(source)

DANN

Benign

0.96

DEOGEN2

Benign

0.095

T;T;.

Eigen

Benign

-0.46

Eigen_PC

Benign

-0.38

FATHMM_MKL

Uncertain

0.88

LIST_S2

Benign

0.85

.;T;D

M_CAP

Benign

0.013

MetaRNN

Benign

0.12

T;T;T

MetaSVM

Benign

-0.94

MutationAssessor

Benign

0.42

N;N;.

PhyloP100

2.9

PrimateAI

Uncertain

0.64

PROVEAN

Benign

-1.9

.;N;.

REVEL

Benign

0.12

Sift

Uncertain

0.0010

.;D;.

Sift4G

Uncertain

0.0040

.;.;D

Polyphen

0.14

B;B;.

Vest4

0.24

MutPred

0.37

Loss of glycosylation at T3600 (P = 0.0338);Loss of glycosylation at T3600 (P = 0.0338);.;

MVP

0.43

MPC

0.31

ClinPred

0.47

GERP RS

4.1

Varity_R

0.28

gMVP

0.76

Mutation Taster

=96/4

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over