NM_012120.3:c.-329C>G

Variant names:

• chr6-47477916-C-G
• rs886061511
• NM_012120.3:c.-329C>G

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS1

The NM_012120.3(CD2AP):​c.-329C>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000324 in 462,568 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: 𝑓 0.000013 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000042 (0 hom.)
• Consequence: CD2AP NM_012120.3 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.124
• 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: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BS1: Variant frequency is greater than expected in population eas. GnomAdExome4 allele frequency = 0.0000417 (13/312068) while in subpopulation EAS AF = 0.000387 (7/18066). AF 95% confidence interval is 0.000181. There are 0 homozygotes in GnomAdExome4. There are 6 alleles in the male GnomAdExome4 subpopulation. Median coverage is 0. This position passed quality control check.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CD2AP	NM_012120.3	MANE Select	c.-329C>G		5_prime_UTR	Exon 1 of 18	NP_036252.1	Q9Y5K6
	CD2AP-DT	NR_187257.1		n.157G>C		non_coding_transcript_exon	Exon 1 of 1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CD2AP	ENST00000359314.5	TSL:1 MANE Select	c.-329C>G		5_prime_UTR	Exon 1 of 18	ENSP00000352264.5	Q9Y5K6
	CD2AP	ENST00000931707.1		c.-329C>G		5_prime_UTR	Exon 1 of 18	ENSP00000601766.1
	CD2AP	ENST00000931708.1		c.-329C>G		5_prime_UTR	Exon 1 of 18	ENSP00000601767.1

Frequencies

GnomAD3 genomes AF: 0.0000133 AC: 2 AN: 150382 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000200

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000148

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.0000417 AC: 13 AN: 312068 Hom.: 0 Cov.: 0 AF XY: 0.0000366 AC XY: 6 AN XY: 163960

African (AFR) AF: 0.00 AC: 0 AN: 6232

American (AMR) AF: 0.00 AC: 0 AN: 11244

Ashkenazi Jewish (ASJ) AF: 0.000104 AC: 1 AN: 9594

East Asian (EAS) AF: 0.000387 AC: 7 AN: 18066

South Asian (SAS) AF: 0.0000557 AC: 2 AN: 35892

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 19890

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1404

European-Non Finnish (NFE) AF: 0.0000157 AC: 3 AN: 191094

Other (OTH) AF: 0.00 AC: 0 AN: 18652

GnomAD4 genome AF: 0.0000133 AC: 2 AN: 150500 Hom.: 0 Cov.: 32 AF XY: 0.0000272 AC XY: 2 AN XY: 73536

African (AFR) AF: 0.00 AC: 0 AN: 41302

American (AMR) AF: 0.00 AC: 0 AN: 15210

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3446

East Asian (EAS) AF: 0.000200 AC: 1 AN: 4988

South Asian (SAS) AF: 0.00 AC: 0 AN: 4670

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10110

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 288

European-Non Finnish (NFE) AF: 0.0000148 AC: 1 AN: 67496

Other (OTH) AF: 0.00 AC: 0 AN: 2094

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000264

Asia WGS AF: 0.000577 AC: 2 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	7.3
DANN	Benign	0.51
PhyloP100		0.12
PromoterAI		0.0057	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: rs886061511; hg19: chr6-47445652;