6-47478053-A-C

Variant names:

• chr6-47478053-A-C
• rs1056434
• NM_012120.3:c.-192A>C

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.-192A>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 0.59 in 701,490 control chromosomes in the GnomAD database, including 123,905 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.58 (25882 hom., cov: 31)
  • Exomes 𝑓: 0.59 (98023 hom.)
• Consequence: CD2AP NM_012120.3 5_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.928
• Publications: 6 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=-0.96).
• BP6: Variant 6-47478053-A-C is Benign according to our data. Variant chr6-47478053-A-C is described in ClinVar as Benign. ClinVar VariationId is 357157.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.796 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.-192A>C		5_prime_UTR	Exon 1 of 18	NP_036252.1	Q9Y5K6
	CD2AP-DT	NR_187257.1		n.20T>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.-192A>C		5_prime_UTR	Exon 1 of 18	ENSP00000352264.5	Q9Y5K6
	CD2AP	ENST00000931707.1		c.-192A>C		5_prime_UTR	Exon 1 of 18	ENSP00000601766.1
	CD2AP	ENST00000931708.1		c.-192A>C		5_prime_UTR	Exon 1 of 18	ENSP00000601767.1

Frequencies

GnomAD3 genomes AF: 0.580 AC: 87936 AN: 151648 Hom.: 25842 Cov.: 31

Gnomad AFR AF: 0.516

Gnomad AMI AF: 0.612

Gnomad AMR AF: 0.675

Gnomad ASJ AF: 0.505

Gnomad EAS AF: 0.817

Gnomad SAS AF: 0.548

Gnomad FIN AF: 0.606

Gnomad MID AF: 0.446

Gnomad NFE AF: 0.582

Gnomad OTH AF: 0.556

GnomAD4 exome AF: 0.592 AC: 325568 AN: 549722 Hom.: 98023 Cov.: 7 AF XY: 0.587 AC XY: 168891 AN XY: 287626

African (AFR) AF: 0.513 AC: 7203 AN: 14048

American (AMR) AF: 0.722 AC: 14958 AN: 20730

Ashkenazi Jewish (ASJ) AF: 0.494 AC: 7363 AN: 14908

East Asian (EAS) AF: 0.812 AC: 25371 AN: 31252

South Asian (SAS) AF: 0.528 AC: 26018 AN: 49254

European-Finnish (FIN) AF: 0.593 AC: 22777 AN: 38382

Middle Eastern (MID) AF: 0.477 AC: 1052 AN: 2206

European-Non Finnish (NFE) AF: 0.583 AC: 203881 AN: 349816

Other (OTH) AF: 0.582 AC: 16945 AN: 29126

GnomAD4 genome AF: 0.580 AC: 88027 AN: 151768 Hom.: 25882 Cov.: 31 AF XY: 0.586 AC XY: 43448 AN XY: 74150

African (AFR) AF: 0.517 AC: 21402 AN: 41414

American (AMR) AF: 0.676 AC: 10336 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.505 AC: 1750 AN: 3466

East Asian (EAS) AF: 0.817 AC: 4148 AN: 5080

South Asian (SAS) AF: 0.548 AC: 2628 AN: 4796

European-Finnish (FIN) AF: 0.606 AC: 6403 AN: 10566

Middle Eastern (MID) AF: 0.438 AC: 127 AN: 290

European-Non Finnish (NFE) AF: 0.582 AC: 39496 AN: 67852

Other (OTH) AF: 0.560 AC: 1181 AN: 2110

Alfa AF: 0.547 Hom.: 6832

Bravo AF: 0.583

Asia WGS AF: 0.686 AC: 2385 AN: 3476

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	-0.96
CADD	Benign	4.0
DANN	Benign	0.38
PhyloP100		-0.93
PromoterAI		0.18	Neutral
RBP_binding_hub_radar		0.92
RBP_regulation_power_radar		2.0
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: rs1056434; hg19: chr6-47445789;