6-47478264-G-C

Variant names:

• chr6-47478264-G-C
• rs370143870
• NM_012120.3:c.4+16G>C

Variant summary

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

The NM_012120.3(CD2AP):​c.4+16G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000706 in 1,416,194 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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: 32)
  • Exomes 𝑓: 7.1e-7 (0 hom.)
• Consequence: CD2AP NM_012120.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.754
• Publications: 0 publications found

Genes affected

CD2AP (HGNC:14258): (CD2 associated protein) This gene encodes a scaffolding molecule that regulates the actin cytoskeleton. The protein directly interacts with filamentous actin and a variety of cell membrane proteins through multiple actin binding sites, SH3 domains, and a proline-rich region containing binding sites for SH3 domains. The cytoplasmic protein localizes to membrane ruffles, lipid rafts, and the leading edges of cells. It is implicated in dynamic actin remodeling and membrane trafficking that occurs during receptor endocytosis and cytokinesis. Haploinsufficiency of this gene is implicated in susceptibility to glomerular disease. [provided by RefSeq, Jul 2008]

CD2AP-DT (HGNC:55263): (CD2AP divergent transcript)

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 (BayesDel_noAF=-0.92).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_012120.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CD2AP	NM_012120.3	MANE Select	c.4+16G>C		intron	N/A	NP_036252.1
	CD2AP-DT	NR_187257.1		n.-192C>G		upstream_gene	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CD2AP	ENST00000359314.5	TSL:1 MANE Select	c.4+16G>C		intron	N/A	ENSP00000352264.5
	CD2AP-DT	ENST00000604014.3	TSL:6	n.-104C>G		upstream_gene	N/A
	CD2AP-DT	ENST00000722837.1		n.-199C>G		upstream_gene	N/A

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.06e-7 AC: 1 AN: 1416194 Hom.: 0 Cov.: 35 AF XY: 0.00 AC XY: 0 AN XY: 700276

African (AFR) AF: 0.00 AC: 0 AN: 32452

American (AMR) AF: 0.00 AC: 0 AN: 37956

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25350

East Asian (EAS) AF: 0.00 AC: 0 AN: 37192

South Asian (SAS) AF: 0.00 AC: 0 AN: 80656

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 48910

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5710

European-Non Finnish (NFE) AF: 9.18e-7 AC: 1 AN: 1089268

Other (OTH) AF: 0.00 AC: 0 AN: 58700

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	9.2
DANN	Benign	0.70
PhyloP100		0.75
PromoterAI		0.22	Neutral

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: rs370143870; hg19: chr6-47446000;