rs1877714

Variant names:

• chr2-218270205-A-C
• rs1877714
• ENST00000691799.1:n.70+485A>C

Your query was ambiguous. Multiple possible variants found:

• chr2-218270205-A-C
• chr2-218270205-A-G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The ENST00000691799.1(PNKD):​n.70+485A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000226 in 1,325,982 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: 34)
  • Exomes 𝑓: 0.0000023 (0 hom.)
• Consequence: PNKD ENST00000691799.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.525
• Publications: 0 publications found

Genes affected

PNKD (HGNC:9153): (PNKD metallo-beta-lactamase domain containing) This gene is thought to play a role in the regulation of myofibrillogenesis. Mutations in this gene have been associated with the movement disorder paroxysmal non-kinesigenic dyskinesia. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Mar 2010]

AAMP (HGNC:18): (angio associated migratory cell protein) The gene is a member of the immunoglobulin superfamily. The encoded protein is associated with angiogenesis, with potential roles in endothelial tube formation and the migration of endothelial cells. It may also regulate smooth muscle cell migration via the RhoA pathway. The encoded protein can bind to heparin and may mediate heparin-sensitive cell adhesion. [provided by RefSeq, Oct 2014]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.67).

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000691799.1. 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
	AAMP	NM_001087.5	MANE Select	c.-119T>G		upstream_gene	N/A	NP_001078.2	Q13685
	AAMP	NM_001302545.2		c.-119T>G		upstream_gene	N/A	NP_001289474.1	C9JEH3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PNKD	ENST00000691799.1		n.70+485A>C		intron	N/A
	AAMP	ENST00000248450.9	TSL:1 MANE Select	c.-119T>G		upstream_gene	N/A	ENSP00000248450.4	Q13685
	AAMP	ENST00000444053.5	TSL:1	c.-119T>G		upstream_gene	N/A	ENSP00000403343.1	C9JEH3

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome AF: 0.00000226 AC: 3 AN: 1325982 Hom.: 0 Cov.: 20 AF XY: 0.00000153 AC XY: 1 AN XY: 653980

African (AFR) AF: 0.00 AC: 0 AN: 29340

American (AMR) AF: 0.00 AC: 0 AN: 30758

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19994

East Asian (EAS) AF: 0.00 AC: 0 AN: 38148

South Asian (SAS) AF: 0.00 AC: 0 AN: 70758

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 47330

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4206

European-Non Finnish (NFE) AF: 0.00000291 AC: 3 AN: 1030608

Other (OTH) AF: 0.00 AC: 0 AN: 54840

GnomAD4 genome Cov.: 34

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.67
CADD	Benign	6.3
DANN	Benign	0.78
PhyloP100		-0.53
PromoterAI		-0.091	Neutral

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: rs1877714; hg19: chr2-219134928;