2-64338218-T-G

Variant names:

• chr2-64338218-T-G
• rs1426699
• ENST00000424119.2:n.318A>C

Variant summary

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

The ENST00000424119.2(ENSG00000238201):​n.318A>C variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.583 in 151,824 control chromosomes in the GnomAD database, including 26,661 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.58 (26659 hom., cov: 30)
  • Exomes 𝑓: 0.63 (2 hom.)
• Consequence: ENSG00000238201 ENST00000424119.2 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.246
• Publications: 1 publications found

Genes affected

ENSG00000238201 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.682 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000424119.2. 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
	LOC105374768	NR_189739.1		n.315A>C		non_coding_transcript_exon	Exon 2 of 3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENSG00000238201	ENST00000424119.2	TSL:1	n.318A>C		non_coding_transcript_exon	Exon 2 of 3
	ENSG00000238201	ENST00000687578.2		n.182-311A>C		intron	N/A
	ENSG00000288932	ENST00000717283.1		n.336-6334T>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.583 AC: 88398 AN: 151690 Hom.: 26631 Cov.: 30

Gnomad AFR AF: 0.689

Gnomad AMI AF: 0.675

Gnomad AMR AF: 0.492

Gnomad ASJ AF: 0.522

Gnomad EAS AF: 0.189

Gnomad SAS AF: 0.533

Gnomad FIN AF: 0.606

Gnomad MID AF: 0.494

Gnomad NFE AF: 0.573

Gnomad OTH AF: 0.523

GnomAD4 exome AF: 0.625 AC: 10 AN: 16 Hom.: 2 Cov.: 0 AF XY: 0.667 AC XY: 8 AN XY: 12

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.625 AC: 10 AN: 16

Other (OTH) AC: 0 AN: 0

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.00819118), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.583 AC: 88473 AN: 151808 Hom.: 26659 Cov.: 30 AF XY: 0.581 AC XY: 43069 AN XY: 74148

African (AFR) AF: 0.689 AC: 28487 AN: 41372

American (AMR) AF: 0.492 AC: 7522 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.522 AC: 1811 AN: 3470

East Asian (EAS) AF: 0.189 AC: 974 AN: 5160

South Asian (SAS) AF: 0.534 AC: 2563 AN: 4796

European-Finnish (FIN) AF: 0.606 AC: 6375 AN: 10524

Middle Eastern (MID) AF: 0.486 AC: 143 AN: 294

European-Non Finnish (NFE) AF: 0.573 AC: 38896 AN: 67900

Other (OTH) AF: 0.517 AC: 1088 AN: 2106

Alfa AF: 0.566 Hom.: 19566

Bravo AF: 0.577

Asia WGS AF: 0.374 AC: 1305 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	1.2
DANN	Benign	0.54
PhyloP100		-0.25

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs1426699; hg19: chr2-64565352;