2-170716799-G-A

Variant names:

• chr2-170716799-G-A
• rs895326913
• NM_001003845.3:c.592G>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001003845.3(SP5):​c.592G>A​(p.Gly198Arg) variant causes a missense change. The variant allele was found at a frequency of 0.00000242 in 1,239,382 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000024 (0 hom.)
• Consequence: SP5 NM_001003845.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.46
• Publications: 0 publications found

Genes affected

SP5 (HGNC:14529): (Sp5 transcription factor) Predicted to enable DNA-binding transcription factor activity, RNA polymerase II-specific and RNA polymerase II cis-regulatory region sequence-specific DNA binding activity. Predicted to be involved in regulation of transcription by RNA polymerase II. Predicted to act upstream of or within bone morphogenesis; cellular response to organic cyclic compound; and post-anal tail morphogenesis. Predicted to be located in nucleus. Predicted to be part of chromatin. [provided by Alliance of Genome Resources, Apr 2022]

ERICH2-DT (HGNC:55686): (ERICH2 divergent transcript)

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.078240484).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001003845.3. 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
	SP5	NM_001003845.3	MANE Select	c.592G>A	p.Gly198Arg	missense	Exon 2 of 2	NP_001003845.1	Q6BEB4
	ERICH2-DT	NR_110185.1		n.376+6705C>T		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SP5	ENST00000375281.4	TSL:1 MANE Select	c.592G>A	p.Gly198Arg	missense	Exon 2 of 2	ENSP00000364430.3	Q6BEB4
	ERICH2-DT	ENST00000662274.1		n.859+6705C>T		intron	N/A
	ERICH2-DT	ENST00000671292.2		n.387+6705C>T		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.0000816 AC: 2 AN: 24524 AF XY: 0.00

Gnomad AFR exome AF: 0.00282

Gnomad AMR exome AF: 0.000305

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000242 AC: 3 AN: 1239382 Hom.: 0 Cov.: 33 AF XY: 0.00000165 AC XY: 1 AN XY: 605950

African (AFR) AF: 0.0000413 AC: 1 AN: 24226

American (AMR) AF: 0.0000765 AC: 1 AN: 13074

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 18198

East Asian (EAS) AF: 0.00 AC: 0 AN: 27288

South Asian (SAS) AF: 0.00 AC: 0 AN: 55220

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 36488

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3516

European-Non Finnish (NFE) AF: 9.90e-7 AC: 1 AN: 1010602

Other (OTH) AF: 0.00 AC: 0 AN: 50770

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.47
BayesDel_addAF	Benign	-0.052	T
BayesDel_noAF	Benign	-0.31
CADD	Benign	19
DANN	Benign	0.88
DEOGEN2	Benign	0.097	T
Eigen	Benign	0.15
Eigen_PC	Benign	0.055
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Benign	0.63	T
M_CAP	Uncertain	0.18	D
MetaRNN	Benign	0.078	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.69	N
PhyloP100		4.5
PrimateAI	Pathogenic	0.93	D
PROVEAN	Benign	-0.58	N
REVEL	Benign	0.25
Sift	Benign	0.57	T
Sift4G	Benign	0.49	T
Polyphen		1.0	D
Vest4		0.27
MutPred		0.25		Gain of methylation at G198 (P = 0.0093)
MVP		0.16
ClinPred		0.069	T
GERP RS		4.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.18
gMVP		0.44
Mutation Taster		=85/15	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: rs895326913; hg19: chr2-171573309;