5-81461092-C-T

Variant names:

• chr5-81461092-C-T
• rs1258676190
• NM_001256732.3:c.674G>A

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001256732.3(SSBP2):​c.674G>A​(p.Gly225Asp) variant causes a missense change. The variant allele was found at a frequency of 0.00000659 in 151,850 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: SSBP2 NM_001256732.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.67

Genes affected

SSBP2 (HGNC:15831): (single stranded DNA binding protein 2) This gene encodes a subunit of a protein complex that interacts with single-stranded DNA and is involved in the DNA damage response and maintenance of genome stability. The encoded protein may also play a role in telomere repair. A variant of this gene may be associated with survival in human glioblastoma patients. [provided by RefSeq, Sep 2016]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SSBP2	NM_001256732.3	c.674G>A	p.Gly225Asp	missense_variant	Exon 10 of 17	ENST00000615665.5	NP_001243661.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SSBP2	ENST00000615665.5	c.674G>A	p.Gly225Asp	missense_variant	Exon 10 of 17	5	NM_001256732.3	ENSP00000483921.1

Frequencies

GnomAD3 genomes AF: 0.00000659 AC: 1 AN: 151850 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000242

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1434758 Hom.: 0 Cov.: 29 AF XY: 0.00 AC XY: 0 AN XY: 712696

Gnomad4 AFR exome AF: 0.00

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 AF: 0.00000659 AC: 1 AN: 151850 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74170

Gnomad4 AFR AF: 0.0000242

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

Alfa AF: 0.0000710 Hom.: 0

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jan 31, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.650G>A (p.G217D) alteration is located in exon 10 (coding exon 10) of the SSBP2 gene. This alteration results from a G to A substitution at nucleotide position 650, causing the glycine (G) at amino acid position 217 to be replaced by an aspartic acid (D). 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	Pathogenic	0.80
BayesDel_addAF	Pathogenic	0.38	D
BayesDel_noAF	Pathogenic	0.31
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.52	D;T;.;.;T;T;.;.
Eigen	Uncertain	0.48
Eigen_PC	Uncertain	0.50
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Benign	0.82	T;T;T;T;T;T;T;T
M_CAP	Benign	0.038	D
MetaRNN	Uncertain	0.54	D;D;D;D;D;D;D;D
MetaSVM	Benign	-0.41	T
MutationAssessor	Uncertain	2.2	M;.;.;.;.;.;.;.
PrimateAI	Uncertain	0.78	T
PROVEAN	Uncertain	-3.2	D;.;D;D;D;D;D;D
REVEL	Benign	0.23
Sift	Benign	0.20	T;.;T;T;T;T;T;T
Sift4G	Uncertain	0.013	D;D;D;D;D;D;D;D
Polyphen		1.0	D;.;.;.;.;.;.;.
Vest4		0.66
MVP		0.32
MPC		1.9
ClinPred		0.98	D
GERP RS		5.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.56
gMVP		0.79

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs1258676190; hg19: chr5-80756911;