chr2-218270205-A-G

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The ENST00000691799.1(PNKD):​n.70+485A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.406 in 1,476,054 control chromosomes in the GnomAD database, including 122,563 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.43 (14391 hom., cov: 34)
  • Exomes 𝑓: 0.40 (108172 hom.)
• Consequence: PNKD ENST00000691799.1 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.525
• Publications: 17 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: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.69).
• BP6: Variant 2-218270205-A-G is Benign according to our data. Variant chr2-218270205-A-G is described in ClinVar as Benign. ClinVar VariationId is 1226098.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.505 is higher than 0.05.

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>C		upstream_gene	N/A	NP_001078.2	Q13685
	AAMP	NM_001302545.2		c.-119T>C		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>G		intron	N/A
	AAMP	ENST00000248450.9	TSL:1 MANE Select	c.-119T>C		upstream_gene	N/A	ENSP00000248450.4	Q13685
	AAMP	ENST00000444053.5	TSL:1	c.-119T>C		upstream_gene	N/A	ENSP00000403343.1	C9JEH3

Frequencies

GnomAD3 genomes AF: 0.431 AC: 65507 AN: 152048 Hom.: 14386 Cov.: 34

Gnomad AFR AF: 0.511

Gnomad AMI AF: 0.429

Gnomad AMR AF: 0.464

Gnomad ASJ AF: 0.393

Gnomad EAS AF: 0.396

Gnomad SAS AF: 0.356

Gnomad FIN AF: 0.290

Gnomad MID AF: 0.519

Gnomad NFE AF: 0.405

Gnomad OTH AF: 0.453

GnomAD4 exome AF: 0.403 AC: 533569 AN: 1323888 Hom.: 108172 Cov.: 20 AF XY: 0.401 AC XY: 262177 AN XY: 653034

African (AFR) AF: 0.516 AC: 15126 AN: 29304

American (AMR) AF: 0.464 AC: 14227 AN: 30694

Ashkenazi Jewish (ASJ) AF: 0.391 AC: 7799 AN: 19964

East Asian (EAS) AF: 0.389 AC: 14824 AN: 38104

South Asian (SAS) AF: 0.354 AC: 25002 AN: 70650

European-Finnish (FIN) AF: 0.305 AC: 14428 AN: 47282

Middle Eastern (MID) AF: 0.499 AC: 2094 AN: 4198

European-Non Finnish (NFE) AF: 0.406 AC: 417498 AN: 1028964

Other (OTH) AF: 0.412 AC: 22571 AN: 54728

GnomAD4 genome AF: 0.431 AC: 65542 AN: 152166 Hom.: 14391 Cov.: 34 AF XY: 0.427 AC XY: 31806 AN XY: 74414

African (AFR) AF: 0.511 AC: 21195 AN: 41504

American (AMR) AF: 0.463 AC: 7084 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.393 AC: 1366 AN: 3472

East Asian (EAS) AF: 0.395 AC: 2043 AN: 5166

South Asian (SAS) AF: 0.357 AC: 1724 AN: 4832

European-Finnish (FIN) AF: 0.290 AC: 3080 AN: 10604

Middle Eastern (MID) AF: 0.517 AC: 152 AN: 294

European-Non Finnish (NFE) AF: 0.405 AC: 27557 AN: 67978

Other (OTH) AF: 0.451 AC: 950 AN: 2106

Alfa AF: 0.424 Hom.: 5322

Bravo AF: 0.448

Asia WGS AF: 0.339 AC: 1176 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.69
CADD	Benign	6.7
DANN	Benign	0.73
PhyloP100		-0.53
PromoterAI		0.0034	Neutral
Mutation Taster		=300/0	polymorphism (auto)

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; COSMIC: COSV50307941; COSMIC: COSV50307941;