NM_020437.5:c.140C>A

Variant names:

• chr22-26433755-C-A
• rs146952882
• NM_020437.5:c.140C>A

Variant summary

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

The NM_020437.5(ASPHD2):​c.140C>A​(p.Ala47Asp) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ASPHD2 NM_020437.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.90

Genes affected

ASPHD2 (HGNC:30437): (aspartate beta-hydroxylase domain containing 2) Predicted to enable dioxygenase activity and metal ion binding activity. Predicted to be involved in peptidyl-amino acid modification. Located in membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ASPHD2	NM_020437.5	c.140C>A	p.Ala47Asp	missense_variant	Exon 2 of 4	ENST00000215906.6	NP_065170.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ASPHD2	ENST00000215906.6	c.140C>A	p.Ala47Asp	missense_variant	Exon 2 of 4	1	NM_020437.5	ENSP00000215906.5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000540 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.45
BayesDel_addAF	Pathogenic	0.28	D
BayesDel_noAF	Pathogenic	0.17
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.025	T
Eigen	Uncertain	0.57
Eigen_PC	Uncertain	0.58
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Benign	0.81	T
M_CAP	Uncertain	0.11	D
MetaRNN	Uncertain	0.73	D
MetaSVM	Benign	-0.60	T
MutationAssessor	Benign	1.8	L
PrimateAI	Uncertain	0.70	T
PROVEAN	Benign	-0.58	N
REVEL	Benign	0.29
Sift	Uncertain	0.0070	D
Sift4G	Uncertain	0.025	D
Polyphen		1.0	D
Vest4		0.81
MutPred		0.32		Gain of relative solvent accessibility (P = 0.0215);
MVP		0.37
MPC		1.8
ClinPred		0.90	D
GERP RS		4.5
Varity_R		0.33
gMVP		0.83

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: rs146952882; hg19: chr22-26829721;