rs879255366

Variant names:

• chr9-110048735-TCCCCCGGAGTCTCCTGGA-T
• rs879255366
• ENST00000434623.6:c.64_81delTCTCCTGGACCCCCGGAG

Your query was ambiguous. Multiple possible variants found:

• chr9-110048735-TCCCCCGGAGTCTCCTGGA-T
• chr9-110048735-TCCCCCGGAGTCTCCTGGA-TCCCCCGGAGTCTCCTGGACCCCCGGAGTCTCCTGGA

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 2P and 16B. PM4 BP6_Very_Strong BA1

The NM_001198656.1(PALM2AKAP2):​c.64_81delTCTCCTGGACCCCCGGAG​(p.Ser22_Glu27del) variant causes a conservative inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0564 in 1,538,218 control chromosomes in the GnomAD database, including 2,885 homozygotes. It is difficult to determine the true allele frequency of this variant because it is of type DEL_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.042 (199 hom., cov: 30)
  • Exomes 𝑓: 0.058 (2686 hom.)
• Consequence: PALM2AKAP2 NM_001198656.1 conservative_inframe_deletion
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.910
• Publications: 1 publications found

Genes affected

PALM2AKAP2 (HGNC:33529): (PALM2 and AKAP2 fusion) This gene belongs to the paralemmin downstream gene (PDG) family defined in PMID:22855693. Paralemmin downstream genes may have evolved contiguously with the paralemmin genes and are associated with other paralemmin paralogs in humans and several other taxa. The gene encodes three distinct protein isoforms, the PALM2 isoform, the AKAP2 isoform and the PALM2-AKAP2 isoform. The biological significance of the PALM2-AKAP2 isoforms is yet unknown. Earlier, PALM2 and AKAP2 were annotated as separate genes and PALM2-AKAP2 was annotated as a readthrough gene. [provided by RefSeq, May 2019]

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• PM4: Nonframeshift variant in NON repetitive region in NM_001198656.1.
• BP6: Variant 9-110048735-TCCCCCGGAGTCTCCTGGA-T is Benign according to our data. Variant chr9-110048735-TCCCCCGGAGTCTCCTGGA-T is described in ClinVar as Benign. ClinVar VariationId is 252563.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.101 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001198656.1. 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
	PALM2AKAP2	NM_007203.5	MANE Select	c.582+32724_582+32741delTCTCCTGGACCCCCGGAG		intron	N/A	NP_009134.1	Q9Y2D5-4
	PALM2AKAP2	NM_001198656.1		c.64_81delTCTCCTGGACCCCCGGAG	p.Ser22_Glu27del	conservative_inframe_deletion	Exon 1 of 5	NP_001185585.1	Q9Y2D5-7
	PALM2AKAP2	NM_001004065.4		c.64_81delTCTCCTGGACCCCCGGAG	p.Ser22_Glu27del	conservative_inframe_deletion	Exon 1 of 4	NP_001004065.2	Q9Y2D5-5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PALM2AKAP2	ENST00000434623.6	TSL:1	c.64_81delTCTCCTGGACCCCCGGAG	p.Ser22_Glu27del	conservative_inframe_deletion	Exon 1 of 5	ENSP00000404782.2	Q9Y2D5-7
	PALM2AKAP2	ENST00000374525.5	TSL:1	c.64_81delTCTCCTGGACCCCCGGAG	p.Ser22_Glu27del	conservative_inframe_deletion	Exon 1 of 4	ENSP00000363649.1	Q9Y2D5-5
	PALM2AKAP2	ENST00000374530.8	TSL:2 MANE Select	c.582+32724_582+32741delTCTCCTGGACCCCCGGAG		intron	N/A	ENSP00000363654.3	Q9Y2D5-4

Frequencies

GnomAD3 genomes AF: 0.0422 AC: 6381 AN: 151304 Hom.: 200 Cov.: 30

Gnomad AFR AF: 0.0124

Gnomad AMI AF: 0.0176

Gnomad AMR AF: 0.0376

Gnomad ASJ AF: 0.0791

Gnomad EAS AF: 0.0516

Gnomad SAS AF: 0.110

Gnomad FIN AF: 0.0148

Gnomad MID AF: 0.0609

Gnomad NFE AF: 0.0584

Gnomad OTH AF: 0.0453

GnomAD2 exomes AF: 0.0395 AC: 5557 AN: 140564 AF XY: 0.0426

Gnomad AFR exome AF: 0.00448

Gnomad AMR exome AF: 0.0200

Gnomad ASJ exome AF: 0.0583

Gnomad EAS exome AF: 0.0343

Gnomad FIN exome AF: 0.0106

Gnomad NFE exome AF: 0.0380

Gnomad OTH exome AF: 0.0487

GnomAD4 exome AF: 0.0580 AC: 80433 AN: 1386798 Hom.: 2686 AF XY: 0.0597 AC XY: 40963 AN XY: 686136

African (AFR) AF: 0.00922 AC: 286 AN: 31018

American (AMR) AF: 0.0279 AC: 1073 AN: 38414

Ashkenazi Jewish (ASJ) AF: 0.0719 AC: 1797 AN: 25004

East Asian (EAS) AF: 0.0527 AC: 1888 AN: 35794

South Asian (SAS) AF: 0.0982 AC: 7810 AN: 79508

European-Finnish (FIN) AF: 0.0228 AC: 794 AN: 34842

Middle Eastern (MID) AF: 0.0919 AC: 385 AN: 4190

European-Non Finnish (NFE) AF: 0.0584 AC: 63090 AN: 1080234

Other (OTH) AF: 0.0573 AC: 3310 AN: 57794

GnomAD4 genome AF: 0.0421 AC: 6371 AN: 151420 Hom.: 199 Cov.: 30 AF XY: 0.0408 AC XY: 3020 AN XY: 74030

African (AFR) AF: 0.0124 AC: 511 AN: 41372

American (AMR) AF: 0.0374 AC: 570 AN: 15224

Ashkenazi Jewish (ASJ) AF: 0.0791 AC: 274 AN: 3464

East Asian (EAS) AF: 0.0510 AC: 259 AN: 5082

South Asian (SAS) AF: 0.109 AC: 523 AN: 4796

European-Finnish (FIN) AF: 0.0148 AC: 157 AN: 10574

Middle Eastern (MID) AF: 0.0655 AC: 19 AN: 290

European-Non Finnish (NFE) AF: 0.0584 AC: 3948 AN: 67612

Other (OTH) AF: 0.0448 AC: 94 AN: 2096

Alfa AF: 0.0221 Hom.: 15

Bravo AF: 0.0405

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.91
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs879255366; hg19: chr9-112811015; COSMIC: COSV57121768;