NM_020877.5:c.10799C>A

Variant names:

• chr17-7819047-C-A
• NM_020877.5:c.10799C>A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_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. 14/21 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 Likely benign.

• Frequency:
  • Genomes: not found (cov: 29)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: DNAH2 NM_020877.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.93

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 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	c.10799C>A	p.Thr3600Asn	missense_variant	Exon 71 of 86	ENST00000572933.6	NP_065928.2

Ensembl

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

Frequencies

GnomAD3 genomes Cov.: 29

GnomAD4 exome AF: 0.00000138 AC: 2 AN: 1453708 Hom.: 0 Cov.: 74 AF XY: 0.00000138 AC XY: 1 AN XY: 723184

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000180

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 29

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	T
BayesDel_noAF	Benign	-0.42
CADD	Benign	18
DANN	Benign	0.96
DEOGEN2	Benign	0.095	T;T;.
Eigen	Benign	-0.46
Eigen_PC	Benign	-0.38
FATHMM_MKL	Uncertain	0.88	D
LIST_S2	Benign	0.85	.;T;D
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.12	T;T;T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	0.42	N;N;.
PrimateAI	Uncertain	0.64	T
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	T
GERP RS		4.1
Varity_R		0.28
gMVP		0.76

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr17-7722365;