6-17507310-G-A

Variant names:

• chr6-17507310-G-A
• NM_006366.3:c.442G>A

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_006366.3(CAP2):​c.442G>A​(p.Val148Met) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,840 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/23 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: CAP2 NM_006366.3 missense, splice_region
• Scores: Splicing: ADA: 0.001152
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.48

Genes affected

CAP2 (HGNC:20039): (cyclase associated actin cytoskeleton regulatory protein 2) This gene was identified by its similarity to the gene for human adenylyl cyclase-associated protein. The function of the protein encoded by this gene is unknown. However, the protein appears to be able to interact with adenylyl cyclase-associated protein and actin. [provided by RefSeq, Jul 2008]

LOC101928491 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.27862233).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CAP2	NM_006366.3	c.442G>A	p.Val148Met	missense_variant, splice_region_variant	Exon 5 of 13	ENST00000229922.7	NP_006357.1
CAP2	NM_001363534.2	c.364G>A	p.Val122Met	missense_variant, splice_region_variant	Exon 4 of 12		NP_001350463.1
CAP2	NM_001363533.2	c.301-31959G>A		intron_variant	Intron 4 of 9		NP_001350462.1
LOC101928491	NR_110855.1	n.282+1263C>T		intron_variant	Intron 2 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CAP2	ENST00000229922.7	c.442G>A	p.Val148Met	missense_variant, splice_region_variant	Exon 5 of 13	1	NM_006366.3	ENSP00000229922.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000205 AC: 3 AN: 1461840 Hom.: 0 Cov.: 32 AF XY: 0.00000275 AC XY: 2 AN XY: 727226

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

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: 0.00000270

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.26
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.48
CADD	Uncertain	24
DANN	Benign	0.78
DEOGEN2	Benign	0.022	T;T;.;.;.
Eigen	Benign	0.076
Eigen_PC	Uncertain	0.23
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Uncertain	0.86	D;T;T;D;T
M_CAP	Benign	0.0054	T
MetaRNN	Benign	0.27	T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.1	L;.;.;.;L
PrimateAI	Uncertain	0.72	T
PROVEAN	Benign	-1.0	N;.;.;N;N
REVEL	Benign	0.080
Sift	Benign	0.38	T;.;.;T;T
Sift4G	Benign	0.27	T;T;T;T;T
Polyphen		0.90	P;.;.;B;.
Vest4		0.27
MutPred		0.74		Gain of catalytic residue at V148 (P = 0.0394);Gain of catalytic residue at V148 (P = 0.0394);Gain of catalytic residue at V148 (P = 0.0394);.;Gain of catalytic residue at V148 (P = 0.0394);
MVP		0.24
MPC		0.71
ClinPred		0.78	D
GERP RS		5.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.13
gMVP		0.55

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.0012
dbscSNV1_RF	Benign	0.010
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

No publications associated with this variant yet.

Other links and lift over

hg19: chr6-17507541;