2-219381413-G-A

Variant names:

• chr2-219381413-G-A
• rs1361567857
• NM_012100.4:c.1161C>T

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 2P and 3B. PM2 BP4_Moderate BP7

The NM_012100.4(DNPEP):​c.1161C>T​(p.Ser387Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000342 in 1,461,894 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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: 33)
  • Exomes 𝑓: 0.0000034 (0 hom.)
• Consequence: DNPEP NM_012100.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.91
• Publications: 0 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: Likely_benign. The variant received -1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.42).
• BP7: Synonymous conserved (PhyloP=2.91 with no splicing effect.

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.1161C>T	p.Ser387Ser	synonymous	Exon 13 of 15	NP_036232.2	Q9ULA0-1
	DNPEP	NM_001319116.2		c.1185C>T	p.Ser395Ser	synonymous	Exon 13 of 15	NP_001306045.1	E7ETB3
	DNPEP	NM_001319118.2		c.1119C>T	p.Ser373Ser	synonymous	Exon 13 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.1161C>T	p.Ser387Ser	synonymous	Exon 13 of 15	ENSP00000273075.4	Q9ULA0-1
	DNPEP	ENST00000523282.6	TSL:2	c.1185C>T	p.Ser395Ser	synonymous	Exon 13 of 15	ENSP00000431076.1	E7ETB3
	DNPEP	ENST00000851982.1		c.1179C>T	p.Ser393Ser	synonymous	Exon 13 of 15	ENSP00000522041.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000342 AC: 5 AN: 1461894 Hom.: 0 Cov.: 33 AF XY: 0.00000275 AC XY: 2 AN XY: 727248

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00000450 AC: 5 AN: 1112012

Other (OTH) AF: 0.00 AC: 0 AN: 60396

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000268340), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.42
CADD	Benign	13
DANN	Benign	0.93
PhyloP100		2.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs1361567857; hg19: chr2-220246135;