chr1-108612187-G-A

Variant names:

• chr1-108612187-G-A
• rs1444990985
• NM_001010883.3:c.298G>A

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001010883.3(EEIG2):​c.298G>A​(p.Ala100Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: EEIG2 NM_001010883.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 8.09
• Publications: 0 publications found

Genes affected

EEIG2 (HGNC:27637): (EEIG family member 2)

ACMG classification

Our verdict: Uncertain_significance. The variant received 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
EEIG2	NM_001010883.3	c.298G>A	p.Ala100Thr	missense_variant	Exon 4 of 11	ENST00000370035.8	NP_001010883.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EEIG2	ENST00000370035.8	c.298G>A	p.Ala100Thr	missense_variant	Exon 4 of 11	1	NM_001010883.3	ENSP00000359052.3
EEIG2	ENST00000405454.1	c.298G>A	p.Ala100Thr	missense_variant	Exon 4 of 11	5		ENSP00000386084.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Mar 21, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.298G>A (p.A100T) alteration is located in exon 4 (coding exon 4) of the FAM102B gene. This alteration results from a G to A substitution at nucleotide position 298, causing the alanine (A) at amino acid position 100 to be replaced by a threonine (T). 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	0.11
BayesDel_addAF	Benign	-0.012	T
BayesDel_noAF	Benign	-0.26
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.045	T;.
Eigen	Uncertain	0.60
Eigen_PC	Uncertain	0.60
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.91	D;D
M_CAP	Benign	0.0099	T
MetaRNN	Uncertain	0.68	D;D
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	1.5	L;L
PhyloP100		8.1
PrimateAI	Pathogenic	0.87	D
PROVEAN	Benign	-0.88	N;N
REVEL	Benign	0.20
Sift	Benign	0.24	T;T
Sift4G	Benign	0.41	T;T
Polyphen		0.99	D;.
Vest4		0.66
MutPred		0.49		Loss of stability (P = 0.0576);Loss of stability (P = 0.0576);
MVP		0.69
MPC		1.1
ClinPred		0.87	D
GERP RS		4.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.19
gMVP		0.66
Mutation Taster		=62/38	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: rs1444990985; hg19: chr1-109154809; COSMIC: COSV64239942;