18-36145968-G-A

Variant names:

• chr18-36145968-G-A
• rs1785928
• NM_018255.4:c.913G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001242875.3(ELP2):​c.1108G>A​(p.Val370Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.355 in 1,611,440 control chromosomes in the GnomAD database, including 103,372 homozygotes. 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.

• Frequency:
  • Genomes: 𝑓 0.36 (9965 hom., cov: 32)
  • Exomes 𝑓: 0.35 (93407 hom.)
• Consequence: ELP2 NM_001242875.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.286
• Publications: 43 publications found

Genes affected

ELP2 (HGNC:18248): (elongator acetyltransferase complex subunit 2) The protein encoded by this gene is a core subunit of the elongator complex, a histone acetyltransferase complex that associates with RNA polymerase II. In addition to histone acetylation, the encoded protein effects transcriptional elongation and may help remodel chromatin. [provided by RefSeq, May 2016]

ELP2 Gene-Disease associations (from GenCC):

• intellectual disability, autosomal recessive 58

  Inheritance: AR Classification: STRONG, MODERATE, LIMITED Submitted by: Ambry Genetics, G2P, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.004386574).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.369 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001242875.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ELP2	NM_018255.4	MANE Select	c.913G>A	p.Val305Met	missense	Exon 10 of 22	NP_060725.1
	ELP2	NM_001242875.3		c.1108G>A	p.Val370Met	missense	Exon 11 of 23	NP_001229804.1
	ELP2	NM_001324466.2		c.1030G>A	p.Val344Met	missense	Exon 10 of 22	NP_001311395.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ELP2	ENST00000358232.11	TSL:1 MANE Select	c.913G>A	p.Val305Met	missense	Exon 10 of 22	ENSP00000350967.6
	ELP2	ENST00000423854.6	TSL:1	c.703G>A	p.Val235Met	missense	Exon 7 of 19	ENSP00000391202.2
	ELP2	ENST00000542824.5	TSL:1	c.835G>A	p.Val279Met	missense	Exon 9 of 20	ENSP00000443800.1

Frequencies

GnomAD3 genomes AF: 0.360 AC: 54740 AN: 151932 Hom.: 9967 Cov.: 32

Gnomad AFR AF: 0.370

Gnomad AMI AF: 0.302

Gnomad AMR AF: 0.370

Gnomad ASJ AF: 0.392

Gnomad EAS AF: 0.198

Gnomad SAS AF: 0.231

Gnomad FIN AF: 0.360

Gnomad MID AF: 0.437

Gnomad NFE AF: 0.372

Gnomad OTH AF: 0.367

GnomAD2 exomes AF: 0.345 AC: 86750 AN: 251140 AF XY: 0.338

Gnomad AFR exome AF: 0.377

Gnomad AMR exome AF: 0.398

Gnomad ASJ exome AF: 0.388

Gnomad EAS exome AF: 0.186

Gnomad FIN exome AF: 0.363

Gnomad NFE exome AF: 0.372

Gnomad OTH exome AF: 0.370

GnomAD4 exome AF: 0.354 AC: 517287 AN: 1459390 Hom.: 93407 Cov.: 33 AF XY: 0.351 AC XY: 254662 AN XY: 726136

African (AFR) AF: 0.378 AC: 12641 AN: 33424

American (AMR) AF: 0.395 AC: 17675 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.398 AC: 10377 AN: 26100

East Asian (EAS) AF: 0.200 AC: 7938 AN: 39664

South Asian (SAS) AF: 0.235 AC: 20253 AN: 86230

European-Finnish (FIN) AF: 0.360 AC: 19237 AN: 53404

Middle Eastern (MID) AF: 0.331 AC: 1905 AN: 5762

European-Non Finnish (NFE) AF: 0.366 AC: 406312 AN: 1109786

Other (OTH) AF: 0.347 AC: 20949 AN: 60298

GnomAD4 genome AF: 0.360 AC: 54751 AN: 152050 Hom.: 9965 Cov.: 32 AF XY: 0.357 AC XY: 26550 AN XY: 74332

African (AFR) AF: 0.370 AC: 15330 AN: 41472

American (AMR) AF: 0.370 AC: 5653 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.392 AC: 1359 AN: 3466

East Asian (EAS) AF: 0.197 AC: 1017 AN: 5172

South Asian (SAS) AF: 0.231 AC: 1116 AN: 4826

European-Finnish (FIN) AF: 0.360 AC: 3801 AN: 10568

Middle Eastern (MID) AF: 0.435 AC: 128 AN: 294

European-Non Finnish (NFE) AF: 0.372 AC: 25301 AN: 67946

Other (OTH) AF: 0.365 AC: 771 AN: 2114

Alfa AF: 0.371 Hom.: 23815

Bravo AF: 0.365

TwinsUK AF: 0.354 AC: 1311

ALSPAC AF: 0.367 AC: 1414

ESP6500AA AF: 0.369 AC: 1626

ESP6500EA AF: 0.371 AC: 3192

ExAC AF: 0.343 AC: 41595

Asia WGS AF: 0.258 AC: 900 AN: 3478

EpiCase AF: 0.371

EpiControl AF: 0.378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.062
BayesDel_addAF	Benign	-0.62	T
BayesDel_noAF	Benign	-0.53
CADD	Benign	4.6
DANN	Benign	0.18
DEOGEN2	Benign	0.017	T
Eigen	Benign	-0.98
Eigen_PC	Benign	-0.80
FATHMM_MKL	Benign	0.37	N
LIST_S2	Benign	0.68	T
MetaRNN	Benign	0.0044	T
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	-1.4	N
PhyloP100		0.29
PrimateAI	Benign	0.30	T
PROVEAN	Benign	1.4	N
REVEL	Benign	0.071
Sift	Benign	0.75	T
Sift4G	Benign	0.93	T
Polyphen		0.0	B
Vest4		0.14
MPC		0.080
ClinPred		0.0011	T
GERP RS		-1.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.023
gMVP		0.18
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs1785928; hg19: chr18-33725931; COSMIC: COSV60848887; COSMIC: COSV60848887;