9-110136296-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_007203.5(PALM2AKAP2):c.752C>T(p.Pro251Leu) variant causes a missense change. The variant allele was found at a frequency of 0.0101 in 1,614,176 control chromosomes in the GnomAD database, including 122 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0084 (5 hom., cov: 32)
  • Exomes 𝑓: 0.010 (117 hom.)
• Consequence: PALM2AKAP2 NM_007203.5 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 3.62

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=0.004045099).
• BP6: Variant 9-110136296-C-T is Benign according to our data. Variant chr9-110136296-C-T is described in ClinVar as [Benign]. Clinvar id is 777836.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.00836 (1274/152314) while in subpopulation SAS AF= 0.022 (106/4818). AF 95% confidence interval is 0.0186. There are 5 homozygotes in gnomad4. There are 659 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 5 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PALM2AKAP2	NM_007203.5	c.752C>T	p.Pro251Leu	missense_variant	8/11	ENST00000374530.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PALM2AKAP2	ENST00000374530.8	c.752C>T	p.Pro251Leu	missense_variant	8/11	2	NM_007203.5

Frequencies

GnomAD3 genomes AF: 0.00836 AC: 1273 AN: 152196 Hom.: 5 Cov.: 32

Gnomad AFR AF: 0.00507

Gnomad AMI AF: 0.0208

Gnomad AMR AF: 0.0120

Gnomad ASJ AF: 0.00173

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0220

Gnomad FIN AF: 0.00367

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.0102

Gnomad OTH AF: 0.00717

GnomAD3 exomes AF: 0.00858 AC: 2135 AN: 248898 Hom.: 17 AF XY: 0.00998 AC XY: 1344 AN XY: 134734

Gnomad AFR exome AF: 0.00443

Gnomad AMR exome AF: 0.00535

Gnomad ASJ exome AF: 0.00238

Gnomad EAS exome AF: 0.000109

Gnomad SAS exome AF: 0.0230

Gnomad FIN exome AF: 0.00374

Gnomad NFE exome AF: 0.00915

Gnomad OTH exome AF: 0.00802

GnomAD4 exome AF: 0.0103 AC: 14994 AN: 1461862 Hom.: 117 Cov.: 32 AF XY: 0.0108 AC XY: 7843 AN XY: 727224

Gnomad4 AFR exome AF: 0.00496

Gnomad4 AMR exome AF: 0.00546

Gnomad4 ASJ exome AF: 0.00199

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.0239

Gnomad4 FIN exome AF: 0.00425

Gnomad4 NFE exome AF: 0.0103

Gnomad4 OTH exome AF: 0.0101

GnomAD4 genome AF: 0.00836 AC: 1274 AN: 152314 Hom.: 5 Cov.: 32 AF XY: 0.00885 AC XY: 659 AN XY: 74476

Gnomad4 AFR AF: 0.00508

Gnomad4 AMR AF: 0.0120

Gnomad4 ASJ AF: 0.00173

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.0220

Gnomad4 FIN AF: 0.00367

Gnomad4 NFE AF: 0.0102

Gnomad4 OTH AF: 0.00710

Alfa AF: 0.00919 Hom.: 14

Bravo AF: 0.00797

TwinsUK AF: 0.00890 AC: 33

ALSPAC AF: 0.0106 AC: 41

ESP6500AA AF: 0.00567 AC: 25

ESP6500EA AF: 0.00953 AC: 82

ExAC AF: 0.00843 AC: 1023

Asia WGS AF: 0.00808 AC: 28 AN: 3478

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

Nov 03, 2017

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.076
BayesDel_addAF	Benign	-0.53	T
BayesDel_noAF	Benign	-0.52
Cadd	Benign	19
Dann	Uncertain	0.99
Eigen	Benign	-0.34
Eigen_PC	Benign	-0.23
FATHMM_MKL	Uncertain	0.84	D
LIST_S2	Benign	0.86	D;D;D;D;D;D
MetaRNN	Benign	0.0040	T;T;T;T;T;T
MetaSVM	Benign	-0.94	T
MutationTaster	Benign	0.75	D;D;D;N;N;N;N
PrimateAI	Benign	0.29	T
PROVEAN	Benign	-1.8	N;N;N;N;D;N
REVEL	Benign	0.028
Sift	Uncertain	0.024	D;.;T;T;D;D
Sift4G	Benign	0.34	T;T;T;T;T;T
Polyphen		0.0040, 0.0	.;.;B;B;B;B
Vest4		0.085
MVP		0.32
MPC		0.092
ClinPred		0.015	T
GERP RS		4.4
Varity_R		0.062
gMVP		0.21

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: rs151065500; hg19: chr9-112898576; COSMIC: COSV99035169; COSMIC: COSV99035169;