rs781513024

Variant names:

• chr10-14881529-G-C
• rs781513024
• NM_001193424.2:c.61G>C

Your query was ambiguous. Multiple possible variants found:

• chr10-14881529-G-C
• chr10-14881529-G-T

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Moderate BS2

The NM_001193424.2(SUV39H2):​c.61G>C​(p.Asp21His) variant causes a missense change. The variant allele was found at a frequency of 0.000039 in 1,591,754 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000059 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000037 (0 hom.)
• Consequence: SUV39H2 NM_001193424.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.64
• Publications: 1 publications found

Genes affected

SUV39H2 (HGNC:17287): (SUV39H2 histone lysine methyltransferase) Enables S-adenosyl-L-methionine binding activity; histone methyltransferase activity (H3-K9 specific); and zinc ion binding activity. Involved in chromatin assembly or disassembly and chromatin remodeling. Acts upstream of or within cellular response to hypoxia and negative regulation of transcription by RNA polymerase II. Located in chromatin. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Likely_benign. The variant received -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.22842035).
• BS2: High AC in GnomAd4 at 9 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001193424.2. 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
	SUV39H2	NM_001193424.2	MANE Select	c.61G>C	p.Asp21His	missense	Exon 2 of 6	NP_001180353.1	Q9H5I1-1
	SUV39H2	NM_001193426.2		c.61G>C	p.Asp21His	missense	Exon 2 of 6	NP_001180355.1	Q9H5I1-3
	SUV39H2	NM_001193425.2		c.-120G>C		5_prime_UTR	Exon 2 of 6	NP_001180354.1	Q9H5I1-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SUV39H2	ENST00000354919.11	TSL:5 MANE Select	c.61G>C	p.Asp21His	missense	Exon 2 of 6	ENSP00000346997.6	Q9H5I1-1
	SUV39H2	ENST00000378325.7	TSL:1	c.61G>C	p.Asp21His	missense	Exon 2 of 6	ENSP00000367576.3	Q9H5I1-3
	SUV39H2	ENST00000313519.9	TSL:1	c.-4+2402G>C		intron	N/A	ENSP00000319208.5	Q9H5I1-2

Frequencies

GnomAD3 genomes AF: 0.0000592 AC: 9 AN: 152086 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000524

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.000478

GnomAD2 exomes AF: 0.0000936 AC: 21 AN: 224376 AF XY: 0.000105

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000476

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000683

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000368 AC: 53 AN: 1439668 Hom.: 0 Cov.: 30 AF XY: 0.0000265 AC XY: 19 AN XY: 715778

African (AFR) AF: 0.0000308 AC: 1 AN: 32426

American (AMR) AF: 0.000443 AC: 18 AN: 40606

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25584

East Asian (EAS) AF: 0.00 AC: 0 AN: 38530

South Asian (SAS) AF: 0.00 AC: 0 AN: 81566

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51920

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5704

European-Non Finnish (NFE) AF: 0.0000254 AC: 28 AN: 1103908

Other (OTH) AF: 0.000101 AC: 6 AN: 59424

GnomAD4 genome AF: 0.0000592 AC: 9 AN: 152086 Hom.: 0 Cov.: 32 AF XY: 0.0000942 AC XY: 7 AN XY: 74288

African (AFR) AF: 0.00 AC: 0 AN: 41418

American (AMR) AF: 0.000524 AC: 8 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5196

South Asian (SAS) AF: 0.00 AC: 0 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10588

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68008

Other (OTH) AF: 0.000478 AC: 1 AN: 2092

Alfa AF: 0.0000712 Hom.: 0

Bravo AF: 0.000125

ExAC AF: 0.0000952 AC: 11

ClinVar

ClinVar submissions as Germline

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	0.31
BayesDel_addAF	Uncertain	0.068	T
BayesDel_noAF	Pathogenic	0.20
CADD	Pathogenic	28
DANN	Uncertain	0.99
DEOGEN2	Benign	0.21	T
Eigen	Uncertain	0.48
Eigen_PC	Uncertain	0.58
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Benign	0.79	T
M_CAP	Uncertain	0.28	D
MetaRNN	Benign	0.23	T
MetaSVM	Pathogenic	1.0	D
MutationAssessor	Benign	1.8	L
PhyloP100		6.6
PrimateAI	Pathogenic	0.88	D
PROVEAN	Benign	-1.1	N
REVEL	Uncertain	0.59
Sift	Uncertain	0.011	D
Sift4G	Uncertain	0.017	D
Polyphen		0.97	D
Vest4		0.31
MutPred		0.32		Gain of helix (P = 0.132)
MVP		0.77
MPC		1.8
ClinPred		0.16	T
GERP RS		5.9
PromoterAI		0.016	Neutral
Varity_R		0.19
gMVP		0.60
Mutation Taster		=72/28	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs781513024; hg19: chr10-14923528; COSMIC: COSV100543125; COSMIC: COSV100543125;