6-47477804-C-A

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_012120.3(CD2AP):​c.-441C>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00725 in 202,014 control chromosomes in the GnomAD database, including 24 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0094 (24 hom., cov: 32)
  • Exomes 𝑓: 0.00058 (0 hom.)
• Consequence: CD2AP NM_012120.3 5_prime_UTR
• Clinical Significance: Benign/Likely 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=-0.83).
• BP6: Variant 6-47477804-C-A is Benign according to our data. Variant chr6-47477804-C-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 357149.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00943 (1435/152176) while in subpopulation AFR AF = 0.0328 (1361/41528). AF 95% confidence interval is 0.0313. There are 24 homozygotes in GnomAd4. There are 689 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 24 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.-441C>A		5_prime_UTR	Exon 1 of 18	NP_036252.1	Q9Y5K6
	CD2AP-DT	NR_187257.1		n.269G>T		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>A		5_prime_UTR	Exon 1 of 18	ENSP00000352264.5	Q9Y5K6
	CD2AP	ENST00000931707.1		c.-441C>A		5_prime_UTR	Exon 1 of 18	ENSP00000601766.1
	CD2AP	ENST00000865252.1		c.-441C>A		5_prime_UTR	Exon 1 of 18	ENSP00000535311.1

Frequencies

GnomAD3 genomes AF: 0.00941 AC: 1431 AN: 152058 Hom.: 25 Cov.: 32

Gnomad AFR AF: 0.0328

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00353

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000118

Gnomad OTH AF: 0.00526

GnomAD4 exome AF: 0.000582 AC: 29 AN: 49838 Hom.: 0 Cov.: 0 AF XY: 0.000691 AC XY: 18 AN XY: 26050

African (AFR) AF: 0.0230 AC: 14 AN: 610

American (AMR) AF: 0.000701 AC: 1 AN: 1426

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 1300

East Asian (EAS) AF: 0.00 AC: 0 AN: 1408

South Asian (SAS) AF: 0.00 AC: 0 AN: 7476

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 2534

Middle Eastern (MID) AF: 0.00935 AC: 2 AN: 214

European-Non Finnish (NFE) AF: 0.000249 AC: 8 AN: 32088

Other (OTH) AF: 0.00144 AC: 4 AN: 2782

GnomAD4 genome AF: 0.00943 AC: 1435 AN: 152176 Hom.: 24 Cov.: 32 AF XY: 0.00926 AC XY: 689 AN XY: 74398

African (AFR) AF: 0.0328 AC: 1361 AN: 41528

American (AMR) AF: 0.00353 AC: 54 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5144

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10604

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.000118 AC: 8 AN: 67986

Other (OTH) AF: 0.00521 AC: 11 AN: 2112

Alfa AF: 0.00 Hom.: 21

ClinVar

ClinVar submissions

Significance: Benign/Likely 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	-0.83
CADD	Benign	6.5
DANN	Benign	0.75
PhyloP100		-0.26
PromoterAI		0.20	Neutral
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: rs111766401; hg19: chr6-47445540;