10-125833792-A-C

Position:

• chr10-125833792-A-C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_078468.3(BCCIP):​c.620A>C​(p.His207Pro) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,854 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: BCCIP NM_078468.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.20

Genes affected

BCCIP (HGNC:978): (BRCA2 and CDKN1A interacting protein) This gene product was isolated on the basis of its interaction with BRCA2 and p21 proteins. It is an evolutionarily conserved nuclear protein with multiple interacting domains. The N-terminal half shares moderate homology with regions of calmodulin and M-calpain, suggesting that it may also bind calcium. Functional studies indicate that this protein may be an important cofactor for BRCA2 in tumor suppression, and a modulator of CDK2 kinase activity via p21. This protein has also been implicated in the regulation of BRCA2 and RAD51 nuclear focus formation, double-strand break-induced homologous recombination, and cell cycle progression. Multiple transcript variants encoding different isoforms have been described for this gene. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.365029).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BCCIP	NM_078468.3	c.620A>C	p.His207Pro	missense_variant	6/7	ENST00000278100.11	NP_510868.1
BCCIP	NM_016567.4	c.620A>C	p.His207Pro	missense_variant	6/8		NP_057651.1
BCCIP	NM_078469.3	c.620A>C	p.His207Pro	missense_variant	6/7		NP_510869.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BCCIP	ENST00000278100.11	c.620A>C	p.His207Pro	missense_variant	6/7	1	NM_078468.3	ENSP00000278100.6
BCCIP	ENST00000368759.5	c.620A>C	p.His207Pro	missense_variant	6/8	1		ENSP00000357748.5
BCCIP	ENST00000299130.7	c.620A>C	p.His207Pro	missense_variant	6/7	1		ENSP00000299130.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461854 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 727226

Gnomad4 AFR exome AF: 0.0000299

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 03, 2022

The c.620A>C (p.H207P) alteration is located in exon 6 (coding exon 6) of the BCCIP gene. This alteration results from a A to C substitution at nucleotide position 620, causing the histidine (H) at amino acid position 207 to be replaced by a proline (P). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Benign	-0.087	T
BayesDel_noAF	Benign	-0.36
CADD	Benign	21
DANN	Benign	0.97
DEOGEN2	Benign	0.059	T;.;.
Eigen	Benign	0.14
Eigen_PC	Benign	0.096
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Uncertain	0.92	D;D;D
M_CAP	Benign	0.026	D
MetaRNN	Benign	0.37	T;T;T
MetaSVM	Benign	-0.88	T
MutationAssessor	Uncertain	2.3	M;M;M
PrimateAI	Benign	0.28	T
PROVEAN	Benign	-2.0	N;N;N
REVEL	Benign	0.11
Sift	Benign	0.17	T;T;T
Sift4G	Benign	0.11	T;T;T
Polyphen		0.77	P;D;D
Vest4		0.42
MutPred		0.41		Gain of phosphorylation at T209 (P = 0.0877);Gain of phosphorylation at T209 (P = 0.0877);Gain of phosphorylation at T209 (P = 0.0877);
MVP		0.48
MPC		0.41
ClinPred		0.63	D
GERP RS		3.5
Varity_R		0.51
gMVP		0.66

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr10-127522361;