NM_007203.5:c.491C>A

Variant names:

• chr9-109932023-C-A
• rs370773077
• NM_007203.5:c.491C>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_007203.5(PALM2AKAP2):​c.491C>A​(p.Ala164Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,459,948 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A164V) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: PALM2AKAP2 NM_007203.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0170
• 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.057000726).

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.491C>A	p.Ala164Glu	missense	Exon 6 of 11	NP_009134.1	Q9Y2D5-4
	PALM2AKAP2	NM_147150.3		c.491C>A	p.Ala164Glu	missense	Exon 6 of 10	NP_671492.1	Q9Y2D5-6
	PALM2AKAP2	NM_053016.6		c.491C>A	p.Ala164Glu	missense	Exon 6 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.491C>A	p.Ala164Glu	missense	Exon 6 of 11	ENSP00000363654.3	Q9Y2D5-4
	PALM2AKAP2	ENST00000314527.9	TSL:1	c.491C>A	p.Ala164Glu	missense	Exon 6 of 7	ENSP00000323805.4	Q9Y2D5-8
	PALM2AKAP2	ENST00000374531.6	TSL:1	c.400+6941C>A		intron	N/A	ENSP00000363656.2	Q9Y2D5-9

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.00000404 AC: 1 AN: 247778 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000290

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1459948 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 725994

African (AFR) AF: 0.00 AC: 0 AN: 33462

American (AMR) AF: 0.0000448 AC: 2 AN: 44648

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26124

East Asian (EAS) AF: 0.00 AC: 0 AN: 39636

South Asian (SAS) AF: 0.00 AC: 0 AN: 86008

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53240

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5706

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1110828

Other (OTH) AF: 0.00 AC: 0 AN: 60296

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.36	T
BayesDel_noAF	Benign	-0.67
CADD	Benign	12
DANN	Benign	0.85
Eigen	Benign	-0.76
Eigen_PC	Benign	-0.64
FATHMM_MKL	Benign	0.18	N
LIST_S2	Benign	0.35	T
M_CAP	Benign	0.0077	T
MetaRNN	Benign	0.057	T
MetaSVM	Benign	-0.99	T
PhyloP100		-0.017
PrimateAI	Benign	0.24	T
PROVEAN	Benign	1.0	N
REVEL	Benign	0.065
Sift	Benign	1.0	T
Sift4G	Benign	0.86	T
Vest4		0.32
MVP		0.24
MPC		0.44
ClinPred		0.57	D
GERP RS		1.5
gMVP		0.14
Mutation Taster		=96/4	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs370773077; hg19: chr9-112694303;