8-25861163-T-C

Variant names:

• chr8-25861163-T-C
• NM_022659.4:c.1228A>G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_022659.4(EBF2):​c.1228A>G​(p.Ser410Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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)
• Consequence: EBF2 NM_022659.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.70

Genes affected

EBF2 (HGNC:19090): (EBF transcription factor 2) The protein encoded by this gene belongs to the COE (Collier/Olf/EBF) family of non-basic, helix-loop-helix transcription factors that have a well conserved DNA binding domain. The COE family proteins play an important role in variety of developmental processes. Studies in mouse suggest that this gene may be involved in the differentiation of osteoblasts. [provided by RefSeq, Oct 2011]

LOC102723395 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.101640314).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EBF2	NM_022659.4	c.1228A>G	p.Ser410Gly	missense_variant	Exon 13 of 16	ENST00000520164.6	NP_073150.2
LOC102723395	XR_001745848.2	n.214-8816T>C		intron_variant	Intron 2 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EBF2	ENST00000520164.6	c.1228A>G	p.Ser410Gly	missense_variant	Exon 13 of 16	2	NM_022659.4	ENSP00000430241.1
EBF2	ENST00000408929.7	c.784A>G	p.Ser262Gly	missense_variant	Exon 12 of 15	2		ENSP00000386178.3
EBF2	ENST00000535548.1	c.421A>G	p.Ser141Gly	missense_variant	Exon 5 of 9	2		ENSP00000437909.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Dec 30, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1228A>G (p.S410G) alteration is located in exon 13 (coding exon 13) of the EBF2 gene. This alteration results from a A to G substitution at nucleotide position 1228, causing the serine (S) at amino acid position 410 to be replaced by a glycine (G). 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	0.064
BayesDel_addAF	Benign	-0.29	T
BayesDel_noAF	Benign	-0.65
CADD	Benign	19
DANN	Uncertain	0.99
DEOGEN2	Benign	0.064	T;T;.
Eigen	Benign	-0.42
Eigen_PC	Benign	-0.20
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Benign	0.77	T;T;T
M_CAP	Benign	0.0090	T
MetaRNN	Benign	0.10	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.0	L;.;.
PrimateAI	Uncertain	0.63	T
PROVEAN	Benign	-0.45	N;N;N
REVEL	Benign	0.078
Sift	Benign	0.31	T;T;T
Sift4G	Benign	0.44	T;T;T
Polyphen		0.0	B;.;.
Vest4		0.079
MutPred		0.26		Loss of phosphorylation at S410 (P = 0.0178);.;.;
MVP		0.37
MPC		0.49
ClinPred		0.63	D
GERP RS		4.1
Varity_R		0.095
gMVP		0.40

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: chr8-25718679;