rs370773077

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr9-109932023-C-A
• chr9-109932023-C-T

Variant summary

Our verdict is Likely benign. Variant got -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. 13/18 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• 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

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 Likely_benign. Variant got -2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PALM2AKAP2	NM_007203.5	c.491C>A	p.Ala164Glu	missense_variant	Exon 6 of 11	ENST00000374530.8	NP_009134.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PALM2AKAP2	ENST00000374530.8	c.491C>A	p.Ala164Glu	missense_variant	Exon 6 of 11	2	NM_007203.5	ENSP00000363654.3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD3 exomes AF: 0.00000404 AC: 1 AN: 247778 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 134060

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 SAS 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

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000448

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
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;T;T;T;T
M_CAP	Benign	0.0077	T
MetaRNN	Benign	0.057	T;T;T;T;T
MetaSVM	Benign	-0.99	T
PrimateAI	Benign	0.24	T
PROVEAN	Benign	1.0	N;N;N;N;N
REVEL	Benign	0.065
Sift	Benign	1.0	T;T;T;T;.
Sift4G	Benign	0.86	T;T;T;T;T
Vest4		0.32
MVP		0.24
MPC		0.44
ClinPred		0.57	D
GERP RS		1.5
gMVP		0.14

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

Publications

LitVar

Other links and lift over

dbSNP: rs370773077; hg19: chr9-112694303;