9-110136428-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_007203.5(PALM2AKAP2):c.884G>A(p.Cys295Tyr) variant causes a missense change. The variant allele was found at a frequency of 0.00375 in 1,614,150 control chromosomes in the GnomAD database, including 173 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.019 (91 hom., cov: 32)
  • Exomes 𝑓: 0.0022 (82 hom.)
• Consequence: PALM2AKAP2 NM_007203.5 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 5.23

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

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0054033697).
• BP6: Variant 9-110136428-G-A is Benign according to our data. Variant chr9-110136428-G-A is described in ClinVar as [Benign]. Clinvar id is 781172.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0625 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PALM2AKAP2	NM_007203.5	c.884G>A	p.Cys295Tyr	missense_variant	8/11	ENST00000374530.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PALM2AKAP2	ENST00000374530.8	c.884G>A	p.Cys295Tyr	missense_variant	8/11	2	NM_007203.5

Frequencies

GnomAD3 genomes AF: 0.0186 AC: 2830 AN: 152140 Hom.: 91 Cov.: 32

Gnomad AFR AF: 0.0645

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00674

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.000426

Gnomad OTH AF: 0.00910

GnomAD3 exomes AF: 0.00506 AC: 1259 AN: 249034 Hom.: 36 AF XY: 0.00381 AC XY: 514 AN XY: 134808

Gnomad AFR exome AF: 0.0652

Gnomad AMR exome AF: 0.00338

Gnomad ASJ exome AF: 0.0000993

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000327

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000539

Gnomad OTH exome AF: 0.00180

GnomAD4 exome AF: 0.00221 AC: 3224 AN: 1461892 Hom.: 82 Cov.: 32 AF XY: 0.00193 AC XY: 1405 AN XY: 727246

Gnomad4 AFR exome AF: 0.0676

Gnomad4 AMR exome AF: 0.00373

Gnomad4 ASJ exome AF: 0.0000765

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000197

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000393

Gnomad4 OTH exome AF: 0.00479

GnomAD4 genome AF: 0.0186 AC: 2836 AN: 152258 Hom.: 91 Cov.: 32 AF XY: 0.0179 AC XY: 1332 AN XY: 74426

Gnomad4 AFR AF: 0.0645

Gnomad4 AMR AF: 0.00673

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000426

Gnomad4 OTH AF: 0.00900

Alfa AF: 0.00370 Hom.: 34

Bravo AF: 0.0209

ESP6500AA AF: 0.0645 AC: 284

ESP6500EA AF: 0.000349 AC: 3

ExAC AF: 0.00623 AC: 756

Asia WGS AF: 0.00375 AC: 13 AN: 3478

EpiCase AF: 0.000654

EpiControl AF: 0.000593

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Dec 31, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.48
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Uncertain	0.080
Cadd	Uncertain	25
Dann	Uncertain	1.0
Eigen	Pathogenic	0.77
Eigen_PC	Pathogenic	0.80
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Uncertain	0.90	D;D;D;D;D;D
MetaRNN	Benign	0.0054	T;T;T;T;T;T
MetaSVM	Benign	-0.81	T
MutationTaster	Benign	1.0	D;D;D;D;D;D;D
PrimateAI	Uncertain	0.67	T
PROVEAN	Uncertain	-3.4	D;D;D;D;D;D
REVEL	Uncertain	0.31
Sift	Pathogenic	0.0	D;.;D;D;D;D
Sift4G	Benign	0.50	T;T;T;T;T;D
Polyphen		0.99, 0.99, 0.96	.;.;D;D;D;D
Vest4		0.82
MVP		0.83
MPC		0.55
ClinPred		0.042	T
GERP RS		6.2
Varity_R		0.74
gMVP		0.36

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

Publications

LitVar

Other links and lift over

dbSNP: rs7039287; hg19: chr9-112898708;