2-64636303-G-C

Variant names:

• chr2-64636303-G-C
• rs760446863
• NM_014755.3:c.569C>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_014755.3(SERTAD2):​c.569C>G​(p.Thr190Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,880 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T190M) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: SERTAD2 NM_014755.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.350
• Publications: 2 publications found

Genes affected

SERTAD2 (HGNC:30784): (SERTA domain containing 2) Predicted to enable transcription coactivator activity. Acts upstream of or within negative regulation of cell growth. Located in cytosol and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.03837049).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014755.3. 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
	SERTAD2	NM_014755.3	MANE Select	c.569C>G	p.Thr190Arg	missense	Exon 2 of 2	NP_055570.1	Q14140

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SERTAD2	ENST00000313349.3	TSL:1 MANE Select	c.569C>G	p.Thr190Arg	missense	Exon 2 of 2	ENSP00000326933.3	Q14140
	SERTAD2	ENST00000859819.1		c.569C>G	p.Thr190Arg	missense	Exon 2 of 2	ENSP00000529878.1
	SERTAD2	ENST00000923255.1		c.569C>G	p.Thr190Arg	missense	Exon 3 of 3	ENSP00000593314.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000398 AC: 1 AN: 251344 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

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: 6.84e-7 AC: 1 AN: 1461880 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 727240

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53406

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1112012

Other (OTH) AF: 0.00 AC: 0 AN: 60396

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.31	T
BayesDel_noAF	Benign	-0.58
CADD	Benign	0.20
DANN	Benign	0.70
DEOGEN2	Benign	0.017	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.29	N
LIST_S2	Benign	0.18	T
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.038	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.34	N
PhyloP100		0.35
PrimateAI	Benign	0.32	T
PROVEAN	Benign	-0.27	N
REVEL	Benign	0.076
Sift	Benign	0.48	T
Sift4G	Benign	0.33	T
Polyphen		0.039	B
Vest4		0.057
MutPred		0.22		Loss of glycosylation at T190 (P = 0.0076)
MVP		0.082
MPC		0.25
ClinPred		0.059	T
GERP RS		-4.6
Varity_R		0.079
gMVP		0.15
Mutation Taster		=98/2	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: rs760446863; hg19: chr2-64863437;