NM_012120.3:c.-441C>G

Variant names:

• chr6-47477804-C-G
• rs111766401
• NM_012120.3:c.-441C>G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_012120.3(CD2AP):​c.-441C>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 0.074 in 201,940 control chromosomes in the GnomAD database, including 636 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.074 (437 hom., cov: 32)
  • Exomes 𝑓: 0.074 (199 hom.)
• Consequence: CD2AP NM_012120.3 5_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.261
• Publications: 3 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant 6-47477804-C-G is Benign according to our data. Variant chr6-47477804-C-G is described in ClinVar as Benign. ClinVar VariationId is 357150.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.125 is higher than 0.05.

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.-441C>G		5_prime_UTR	Exon 1 of 18	NP_036252.1	Q9Y5K6
	CD2AP-DT	NR_187257.1		n.269G>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.-441C>G		5_prime_UTR	Exon 1 of 18	ENSP00000352264.5	Q9Y5K6
	CD2AP	ENST00000931707.1		c.-441C>G		5_prime_UTR	Exon 1 of 18	ENSP00000601766.1
	CD2AP	ENST00000865252.1		c.-441C>G		5_prime_UTR	Exon 1 of 18	ENSP00000535311.1

Frequencies

GnomAD3 genomes AF: 0.0740 AC: 11251 AN: 152038 Hom.: 436 Cov.: 32

Gnomad AFR AF: 0.0629

Gnomad AMI AF: 0.0769

Gnomad AMR AF: 0.0756

Gnomad ASJ AF: 0.118

Gnomad EAS AF: 0.0774

Gnomad SAS AF: 0.134

Gnomad FIN AF: 0.0546

Gnomad MID AF: 0.0633

Gnomad NFE AF: 0.0765

Gnomad OTH AF: 0.0789

GnomAD4 exome AF: 0.0739 AC: 3681 AN: 49784 Hom.: 199 Cov.: 0 AF XY: 0.0790 AC XY: 2055 AN XY: 26022

African (AFR) AF: 0.0541 AC: 33 AN: 610

American (AMR) AF: 0.0653 AC: 93 AN: 1424

Ashkenazi Jewish (ASJ) AF: 0.0918 AC: 119 AN: 1296

East Asian (EAS) AF: 0.0703 AC: 99 AN: 1408

South Asian (SAS) AF: 0.112 AC: 838 AN: 7466

European-Finnish (FIN) AF: 0.0621 AC: 157 AN: 2530

Middle Eastern (MID) AF: 0.0607 AC: 13 AN: 214

European-Non Finnish (NFE) AF: 0.0665 AC: 2131 AN: 32056

Other (OTH) AF: 0.0712 AC: 198 AN: 2780

GnomAD4 genome AF: 0.0740 AC: 11266 AN: 152156 Hom.: 437 Cov.: 32 AF XY: 0.0748 AC XY: 5564 AN XY: 74388

African (AFR) AF: 0.0631 AC: 2618 AN: 41518

American (AMR) AF: 0.0756 AC: 1157 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.118 AC: 411 AN: 3470

East Asian (EAS) AF: 0.0774 AC: 398 AN: 5144

South Asian (SAS) AF: 0.133 AC: 643 AN: 4820

European-Finnish (FIN) AF: 0.0546 AC: 579 AN: 10604

Middle Eastern (MID) AF: 0.0612 AC: 18 AN: 294

European-Non Finnish (NFE) AF: 0.0765 AC: 5202 AN: 67984

Other (OTH) AF: 0.0805 AC: 170 AN: 2112

Alfa AF: 0.0325 Hom.: 21

Bravo AF: 0.0729

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	Focal segmental glomerulosclerosis 3, susceptibility to (1)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	6.7
DANN	Benign	0.71
PhyloP100		-0.26
PromoterAI		0.32	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=300/0	polymorphism (auto)

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: rs111766401; hg19: chr6-47445540;