2-219384394-T-G

Variant names:

• chr2-219384394-T-G
• rs1469160488
• NM_012100.4:c.824A>C

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_012100.4(DNPEP):​c.824A>C​(p.Asn275Thr) variant causes a missense change involving the alteration of a conserved nucleotide. 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. N275S) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: DNPEP NM_012100.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.75
• Publications: 1 publications found

Genes affected

DNPEP (HGNC:2981): (aspartyl aminopeptidase) The protein encoded by this gene is an aminopeptidase which prefers acidic amino acids, and specifically favors aspartic acid over glutamic acid. It is thought to be a cytosolic protein involved in general metabolism of intracellular proteins. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jan 2016]

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_012100.4. 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
	DNPEP	NM_012100.4	MANE Select	c.824A>C	p.Asn275Thr	missense	Exon 9 of 15	NP_036232.2	Q9ULA0-1
	DNPEP	NM_001319116.2		c.848A>C	p.Asn283Thr	missense	Exon 9 of 15	NP_001306045.1	E7ETB3
	DNPEP	NM_001319118.2		c.782A>C	p.Asn261Thr	missense	Exon 9 of 15	NP_001306047.1	E5RIA4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNPEP	ENST00000273075.9	TSL:1 MANE Select	c.824A>C	p.Asn275Thr	missense	Exon 9 of 15	ENSP00000273075.4	Q9ULA0-1
	DNPEP	ENST00000523282.6	TSL:2	c.848A>C	p.Asn283Thr	missense	Exon 9 of 15	ENSP00000431076.1	E7ETB3
	DNPEP	ENST00000851982.1		c.842A>C	p.Asn281Thr	missense	Exon 9 of 15	ENSP00000522041.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.95
BayesDel_addAF	Pathogenic	0.39	D
BayesDel_noAF	Uncertain	0.070
CADD	Pathogenic	29
DANN	Uncertain	1.0
DEOGEN2	Benign	0.0075	T
Eigen	Pathogenic	0.97
Eigen_PC	Pathogenic	0.83
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Benign	0.21	T
M_CAP	Pathogenic	0.54	D
MetaRNN	Uncertain	0.74	D
MetaSVM	Uncertain	0.71	D
PhyloP100		7.7
PROVEAN	Benign	0.23	N
REVEL	Benign	0.23
Sift	Benign	0.29	T
MutPred		0.56		Loss of sheet (P = 0.0181)
MVP		0.80
ClinPred		1.0	D
GERP RS		4.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=3/97	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: rs1469160488; hg19: chr2-220249116;