chr2-174336887-T-A

Variant names:

• chr2-174336887-T-A
• NM_001145250.2:c.802T>A

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 3P and 4B. PM2 PP2 BP4_Strong

The NM_001145250.2(SP9):​c.802T>A​(p.Ser268Thr) 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. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: SP9 NM_001145250.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.0770
• Publications: 0 publications found

Genes affected

SP9 (HGNC:30690): (Sp9 transcription factor) Enables sequence-specific double-stranded DNA binding activity. Predicted to be involved in regulation of transcription by RNA polymerase II. Predicted to be located in nucleus. Predicted to be part of chromatin. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000280414 (HGNC:):

LINC01305 (HGNC:27690): (long intergenic non-protein coding RNA 1305)

ACMG classification

Our verdict: Likely_benign. The variant received -1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP2: Missense variant in the gene, where a lot of missense mutations are associated with disease in ClinVar. The gene has 2 curated pathogenic missense variants (we use a threshold of 10). The gene has 0 curated benign missense variants. Gene score misZ: 2.2641 (below the threshold of 3.09). Trascript score misZ: 0.44683 (below the threshold of 3.09). GenCC associations: The gene is linked to complex neurodevelopmental disorder.
• BP4: Computational evidence support a benign effect (MetaRNN=0.028471649).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001145250.2. 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
	SP9	NM_001145250.2	MANE Select	c.802T>A	p.Ser268Thr	missense	Exon 2 of 2	NP_001138722.1	P0CG40

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SP9	ENST00000394967.3	TSL:5 MANE Select	c.802T>A	p.Ser268Thr	missense	Exon 2 of 2	ENSP00000378418.2	P0CG40
	ENSG00000280414	ENST00000624790.1	TSL:6	n.680A>T		non_coding_transcript_exon	Exon 1 of 1
	LINC01305	ENST00000823786.1		n.619-4199T>A		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 35

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.36	T
BayesDel_noAF	Benign	-0.76
CADD	Benign	20
DANN	Benign	0.91
DEOGEN2	Benign	0.0097	T
Eigen	Benign	-0.69
Eigen_PC	Benign	-0.50
FATHMM_MKL	Benign	0.47	N
LIST_S2	Benign	0.49	T
M_CAP	Uncertain	0.22	D
MetaRNN	Benign	0.028	T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	-0.79	N
PhyloP100		0.077
PrimateAI	Pathogenic	0.94	D
PROVEAN	Benign	-0.060	N
REVEL	Benign	0.019
Sift	Benign	1.0	T
Sift4G	Benign	0.74	T
Polyphen		0.021	B
Vest4		0.048
MutPred		0.33		Gain of loop (P = 0.0435)
MVP		0.030
MPC		1.2
ClinPred		0.071	T
GERP RS		1.9
Varity_R		0.063
gMVP		0.38
Mutation Taster		=96/4	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

hg19: chr2-175201615;