rs146952882

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr22-26433755-C-A
• chr22-26433755-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A47V) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ASPHD2 NM_020437.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.90
• Publications: 1 publications found

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

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020437.5. 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
	ASPHD2	NM_020437.5	MANE Select	c.140C>A	p.Ala47Asp	missense	Exon 2 of 4	NP_065170.2	Q6ICH7

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ASPHD2	ENST00000215906.6	TSL:1 MANE Select	c.140C>A	p.Ala47Asp	missense	Exon 2 of 4	ENSP00000215906.5	Q6ICH7
	ASPHD2	ENST00000851348.1		c.140C>A	p.Ala47Asp	missense	Exon 2 of 4	ENSP00000521407.1
	ASPHD2	ENST00000851349.1		c.140C>A	p.Ala47Asp	missense	Exon 1 of 3	ENSP00000521408.1

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 v4.9

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
PhyloP100		6.9
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
Mutation Taster		=42/58	disease causing

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

Other links and lift over

dbSNP: rs146952882; hg19: chr22-26829721;