NM_007203.5:c.386C>T

Variant names:

• chr9-109925074-C-T
• rs150674445
• NM_007203.5:c.386C>T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_007203.5(PALM2AKAP2):​c.386C>T​(p.Thr129Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000612 in 1,614,014 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T129K) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.00022 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00065 (0 hom.)
• Consequence: PALM2AKAP2 NM_007203.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.25
• Publications: 9 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: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.030702353).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_007203.5. 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.386C>T	p.Thr129Met	missense	Exon 5 of 11	NP_009134.1	Q9Y2D5-4
	PALM2AKAP2	NM_147150.3		c.386C>T	p.Thr129Met	missense	Exon 5 of 10	NP_671492.1	Q9Y2D5-6
	PALM2AKAP2	NM_053016.6		c.386C>T	p.Thr129Met	missense	Exon 5 of 7	NP_443749.5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PALM2AKAP2	ENST00000374530.8	TSL:2 MANE Select	c.386C>T	p.Thr129Met	missense	Exon 5 of 11	ENSP00000363654.3	Q9Y2D5-4
	PALM2AKAP2	ENST00000314527.9	TSL:1	c.386C>T	p.Thr129Met	missense	Exon 5 of 7	ENSP00000323805.4	Q9Y2D5-8
	PALM2AKAP2	ENST00000374531.6	TSL:1	c.392C>T	p.Thr131Met	missense	Exon 6 of 7	ENSP00000363656.2	Q9Y2D5-9

Frequencies

GnomAD3 genomes AF: 0.000224 AC: 34 AN: 152048 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000725

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000622

Gnomad FIN AF: 0.000189

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000382

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000265 AC: 66 AN: 249020 AF XY: 0.000237

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000116

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000109

Gnomad FIN exome AF: 0.0000462

Gnomad NFE exome AF: 0.000530

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000652 AC: 953 AN: 1461848 Hom.: 0 Cov.: 30 AF XY: 0.000626 AC XY: 455 AN XY: 727228

African (AFR) AF: 0.0000597 AC: 2 AN: 33480

American (AMR) AF: 0.0000894 AC: 4 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39696

South Asian (SAS) AF: 0.0000812 AC: 7 AN: 86256

European-Finnish (FIN) AF: 0.000187 AC: 10 AN: 53416

Middle Eastern (MID) AF: 0.000520 AC: 3 AN: 5768

European-Non Finnish (NFE) AF: 0.000823 AC: 915 AN: 1111978

Other (OTH) AF: 0.000182 AC: 11 AN: 60394

GnomAD4 genome AF: 0.000223 AC: 34 AN: 152166 Hom.: 0 Cov.: 32 AF XY: 0.000215 AC XY: 16 AN XY: 74394

African (AFR) AF: 0.0000723 AC: 3 AN: 41504

American (AMR) AF: 0.00 AC: 0 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5170

South Asian (SAS) AF: 0.000623 AC: 3 AN: 4816

European-Finnish (FIN) AF: 0.000189 AC: 2 AN: 10584

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000382 AC: 26 AN: 68012

Other (OTH) AF: 0.00 AC: 0 AN: 2114

Alfa AF: 0.000456 Hom.: 0

Bravo AF: 0.000238

TwinsUK AF: 0.000539 AC: 2

ALSPAC AF: 0.000259 AC: 1

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000465 AC: 4

ExAC AF: 0.000272 AC: 33

EpiCase AF: 0.000273

EpiControl AF: 0.000474

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.092
BayesDel_addAF	Benign	-0.39	T
BayesDel_noAF	Benign	-0.45
CADD	Benign	20
DANN	Uncertain	1.0
DEOGEN2	Benign	0.021	T
Eigen	Benign	0.18
Eigen_PC	Uncertain	0.25
FATHMM_MKL	Benign	0.63	D
LIST_S2	Benign	0.71	T
M_CAP	Benign	0.0043	T
MetaRNN	Benign	0.031	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.39	N
PhyloP100		1.2
PrimateAI	Benign	0.38	T
PROVEAN	Benign	0.40	N
REVEL	Benign	0.088
Sift	Benign	0.58	T
Sift4G	Benign	0.19	T
Polyphen		0.66	P
Vest4		0.26
MVP		0.31
MPC		0.50
ClinPred		0.084	T
GERP RS		4.5
Varity_R		0.032
gMVP		0.16
Mutation Taster		=91/9	polymorphism

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: rs150674445; hg19: chr9-112687354; COSMIC: COSV57111820; COSMIC: COSV57111820;