rs2236074

Variant names:

• chr1-27884873-G-A
• rs2236074
• NM_001105556.3:c.1720-422G>A

Variant summary

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

The NM_001105556.3(THEMIS2):​c.1720-422G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.383 in 169,412 control chromosomes in the GnomAD database, including 12,601 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 0.38 (11256 hom., cov: 32)
  • Exomes 𝑓: 0.39 (1345 hom.)
• Consequence: THEMIS2 NM_001105556.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0130
• Publications: 5 publications found

Genes affected

THEMIS2 (HGNC:16839): (thymocyte selection associated family member 2) Predicted to be involved in T cell receptor signaling pathway and regulation of B cell activation. Predicted to be active in cytoplasm and nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.429 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001105556.3. 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
	THEMIS2	NM_001105556.3	MANE Select	c.1720-422G>A		intron	N/A	NP_001099026.1
	THEMIS2	NM_001286113.2		c.1333-422G>A		intron	N/A	NP_001273042.1
	THEMIS2	NM_001286115.2		c.1132-422G>A		intron	N/A	NP_001273044.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	THEMIS2	ENST00000373921.8	TSL:5 MANE Select	c.1720-422G>A		intron	N/A	ENSP00000363031.3
	THEMIS2	ENST00000456990.1	TSL:1	c.961-422G>A		intron	N/A	ENSP00000398049.1
	THEMIS2	ENST00000373925.5	TSL:1	c.647-422G>A		intron	N/A	ENSP00000363035.1

Frequencies

GnomAD3 genomes AF: 0.383 AC: 58127 AN: 151920 Hom.: 11241 Cov.: 32

Gnomad AFR AF: 0.400

Gnomad AMI AF: 0.549

Gnomad AMR AF: 0.401

Gnomad ASJ AF: 0.351

Gnomad EAS AF: 0.443

Gnomad SAS AF: 0.339

Gnomad FIN AF: 0.378

Gnomad MID AF: 0.434

Gnomad NFE AF: 0.366

Gnomad OTH AF: 0.384

GnomAD4 exome AF: 0.390 AC: 6781 AN: 17374 Hom.: 1345 Cov.: 0 AF XY: 0.382 AC XY: 3707 AN XY: 9698

African (AFR) AF: 0.469 AC: 60 AN: 128

American (AMR) AF: 0.496 AC: 528 AN: 1064

Ashkenazi Jewish (ASJ) AF: 0.388 AC: 93 AN: 240

East Asian (EAS) AF: 0.478 AC: 151 AN: 316

South Asian (SAS) AF: 0.338 AC: 1392 AN: 4120

European-Finnish (FIN) AF: 0.420 AC: 268 AN: 638

Middle Eastern (MID) AF: 0.423 AC: 22 AN: 52

European-Non Finnish (NFE) AF: 0.393 AC: 3940 AN: 10014

Other (OTH) AF: 0.408 AC: 327 AN: 802

GnomAD4 genome AF: 0.383 AC: 58176 AN: 152038 Hom.: 11256 Cov.: 32 AF XY: 0.379 AC XY: 28191 AN XY: 74326

African (AFR) AF: 0.400 AC: 16589 AN: 41444

American (AMR) AF: 0.402 AC: 6141 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.351 AC: 1219 AN: 3470

East Asian (EAS) AF: 0.444 AC: 2295 AN: 5172

South Asian (SAS) AF: 0.337 AC: 1627 AN: 4828

European-Finnish (FIN) AF: 0.378 AC: 4001 AN: 10574

Middle Eastern (MID) AF: 0.446 AC: 131 AN: 294

European-Non Finnish (NFE) AF: 0.366 AC: 24871 AN: 67952

Other (OTH) AF: 0.379 AC: 801 AN: 2112

Alfa AF: 0.370 Hom.: 6606

Bravo AF: 0.393

Asia WGS AF: 0.339 AC: 1176 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.85
DANN	Benign	0.63
PhyloP100		0.013
Mutation Taster		=100/0	polymorphism (auto)

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: rs2236074; hg19: chr1-28211384;