rs9369697

Variant names:

• chr6-47477948-G-C
• rs9369697
• NM_012120.3:c.-297G>C

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_012120.3(CD2AP):​c.-297G>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00359 in 516,748 control chromosomes in the GnomAD database, including 41 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0046 (16 hom., cov: 32)
  • Exomes 𝑓: 0.0032 (25 hom.)
• Consequence: CD2AP NM_012120.3 5_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.63
• 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant 6-47477948-G-C is Benign according to our data. Variant chr6-47477948-G-C is described in ClinVar as Benign. ClinVar VariationId is 357154.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population amr. GnomAd4 allele frequency = 0.00464 (705/152002) while in subpopulation AMR AF = 0.0314 (480/15284). AF 95% confidence interval is 0.0291. There are 16 homozygotes in GnomAd4. There are 393 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 16 AD,AR gene

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.-297G>C		5_prime_UTR	Exon 1 of 18	NP_036252.1	Q9Y5K6
	CD2AP-DT	NR_187257.1		n.125C>G		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.-297G>C		5_prime_UTR	Exon 1 of 18	ENSP00000352264.5	Q9Y5K6
	CD2AP	ENST00000931707.1		c.-297G>C		5_prime_UTR	Exon 1 of 18	ENSP00000601766.1
	CD2AP	ENST00000931708.1		c.-297G>C		5_prime_UTR	Exon 1 of 18	ENSP00000601767.1

Frequencies

GnomAD3 genomes AF: 0.00464 AC: 705 AN: 151888 Hom.: 16 Cov.: 32

Gnomad AFR AF: 0.00106

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0314

Gnomad ASJ AF: 0.00260

Gnomad EAS AF: 0.0203

Gnomad SAS AF: 0.00145

Gnomad FIN AF: 0.00302

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000295

Gnomad OTH AF: 0.00431

GnomAD4 exome AF: 0.00315 AC: 1150 AN: 364746 Hom.: 25 Cov.: 0 AF XY: 0.00270 AC XY: 518 AN XY: 192102

African (AFR) AF: 0.000271 AC: 2 AN: 7380

American (AMR) AF: 0.0464 AC: 634 AN: 13672

Ashkenazi Jewish (ASJ) AF: 0.00254 AC: 28 AN: 11030

East Asian (EAS) AF: 0.0127 AC: 289 AN: 22736

South Asian (SAS) AF: 0.000731 AC: 29 AN: 39666

European-Finnish (FIN) AF: 0.00217 AC: 53 AN: 24388

Middle Eastern (MID) AF: 0.000614 AC: 1 AN: 1628

European-Non Finnish (NFE) AF: 0.000229 AC: 51 AN: 222680

Other (OTH) AF: 0.00292 AC: 63 AN: 21566

GnomAD4 genome AF: 0.00464 AC: 705 AN: 152002 Hom.: 16 Cov.: 32 AF XY: 0.00529 AC XY: 393 AN XY: 74320

African (AFR) AF: 0.00106 AC: 44 AN: 41500

American (AMR) AF: 0.0314 AC: 480 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.00260 AC: 9 AN: 3462

East Asian (EAS) AF: 0.0204 AC: 105 AN: 5150

South Asian (SAS) AF: 0.00125 AC: 6 AN: 4814

European-Finnish (FIN) AF: 0.00302 AC: 32 AN: 10592

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 292

European-Non Finnish (NFE) AF: 0.000295 AC: 20 AN: 67886

Other (OTH) AF: 0.00426 AC: 9 AN: 2112

Alfa AF: 0.00328 Hom.: 2

Bravo AF: 0.00791

Asia WGS AF: 0.0140 AC: 50 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	Focal segmental glomerulosclerosis 3, susceptibility to (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	12
DANN	Benign	0.82
PhyloP100		2.6
PromoterAI		-0.034	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=300/0	polymorphism

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: rs9369697; hg19: chr6-47445684;