rs200709517

Variant names:

• chr17-7733193-C-A
• rs200709517
• NM_020877.5:c.506C>A

Your query was ambiguous. Multiple possible variants found:

• chr17-7733193-C-A
• chr17-7733193-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_020877.5(DNAH2):​c.506C>A​(p.Pro169Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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.

• Frequency: Genomes: not found (cov: 31)
• Consequence: DNAH2 NM_020877.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.50

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=0.1325404).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNAH2	NM_020877.5	c.506C>A	p.Pro169Gln	missense_variant	Exon 5 of 86	ENST00000572933.6	NP_065928.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DNAH2	ENST00000572933.6	c.506C>A	p.Pro169Gln	missense_variant	Exon 5 of 86	2	NM_020877.5	ENSP00000458355.1
DNAH2	ENST00000570791.5	c.506C>A	p.Pro169Gln	missense_variant	Exon 5 of 14	1		ENSP00000460245.1
DNAH2	ENST00000389173.6	c.506C>A	p.Pro169Gln	missense_variant	Exon 4 of 85	2		ENSP00000373825.2

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD3 exomes AF: 0.00000398 AC: 1 AN: 251454 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 135900

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000879

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.42
CADD	Benign	18
DANN	Benign	0.91
DEOGEN2	Benign	0.017	T;.;T
Eigen	Benign	-0.24
Eigen_PC	Benign	-0.013
FATHMM_MKL	Benign	0.54	D
LIST_S2	Benign	0.73	.;T;T
M_CAP	Benign	0.0088	T
MetaRNN	Benign	0.13	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.82	L;L;L
PrimateAI	Uncertain	0.51	T
PROVEAN	Benign	-0.080	.;.;N
REVEL	Benign	0.14
Sift	Benign	0.30	.;.;T
Sift4G	Uncertain	0.043	.;D;.
Polyphen		0.012	B;B;B
Vest4		0.29
MutPred		0.44		Gain of catalytic residue at P169 (P = 0.0829);Gain of catalytic residue at P169 (P = 0.0829);Gain of catalytic residue at P169 (P = 0.0829);
MVP		0.39
MPC		0.18
ClinPred		0.13	T
GERP RS		5.4
Varity_R		0.050
gMVP		0.22

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

LitVar

Other links and lift over

dbSNP: rs200709517; hg19: chr17-7636511;