2-170716823-G-C

Position:

• chr2-170716823-G-C

Variant summary

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

The NM_001003845.3(SP5):​c.616G>C​(p.Gly206Arg) 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: SP5 NM_001003845.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.51

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

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=0.18208638).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SP5	NM_001003845.3	c.616G>C	p.Gly206Arg	missense_variant	2/2	ENST00000375281.4	NP_001003845.1
ERICH2-DT	NR_110185.1	n.376+6681C>G		intron_variant, non_coding_transcript_variant
SP5	XM_005246542.5	c.748G>C	p.Gly250Arg	missense_variant	2/2		XP_005246599.1
SP5	XM_047444264.1	c.388G>C	p.Gly130Arg	missense_variant	2/2		XP_047300220.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SP5	ENST00000375281.4	c.616G>C	p.Gly206Arg	missense_variant	2/2	1	NM_001003845.3	ENSP00000364430	P1
ERICH2-DT	ENST00000662274.1	n.859+6681C>G		intron_variant, non_coding_transcript_variant
ERICH2-DT	ENST00000671292.1	n.336+6681C>G		intron_variant, non_coding_transcript_variant
ERICH2-DT	ENST00000690230.1	n.404+6681C>G		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 33

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

Aug 02, 2021

The c.616G>C (p.G206R) alteration is located in exon 2 (coding exon 2) of the SP5 gene. This alteration results from a G to C substitution at nucleotide position 616, causing the glycine (G) at amino acid position 206 to be replaced by an arginine (R). 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	Uncertain	0.49
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.52
CADD	Uncertain	24
DANN	Benign	0.96
DEOGEN2	Benign	0.26	T
Eigen	Benign	-0.34
Eigen_PC	Benign	-0.30
FATHMM_MKL	Benign	0.50	N
LIST_S2	Benign	0.55	T
M_CAP	Uncertain	0.20	D
MetaRNN	Benign	0.18	T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	-0.90	N
MutationTaster	Benign	1.0	N
PrimateAI	Pathogenic	0.92	D
PROVEAN	Benign	-0.64	N
REVEL	Benign	0.062
Sift	Benign	0.15	T
Sift4G	Benign	0.36	T
Polyphen		0.84	P
Vest4		0.38
MutPred		0.29		Gain of methylation at G206 (P = 0.0172);
MVP		0.12
ClinPred		0.61	D
GERP RS		4.2
Varity_R		0.099
gMVP		0.44

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: chr2-171573333;