chr2-223993926-G-A

Variant names:

• chr2-223993926-G-A
• rs6721140
• NM_001136528.2:c.488-1926C>T

Variant summary

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

The NM_001136528.2(SERPINE2):​c.488-1926C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.621 in 152,006 control chromosomes in the GnomAD database, including 29,770 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 0.62 (29770 hom., cov: 32)
• Consequence: SERPINE2 NM_001136528.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.993
• Publications: 7 publications found

Genes affected

SERPINE2 (HGNC:8951): (serpin family E member 2) This gene encodes a member of the serpin family of proteins, a group of proteins that inhibit serine proteases. Thrombin, urokinase, plasmin and trypsin are among the proteases that this family member can inhibit. This gene is a susceptibility gene for chronic obstructive pulmonary disease and for emphysema. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Aug 2012]

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 (AMR) allele frequency at 95% confidence interval = 0.703 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001136528.2. 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
	SERPINE2	NM_001136528.2	MANE Select	c.488-1926C>T		intron	N/A	NP_001130000.1
	SERPINE2	NM_001136530.1		c.524-1926C>T		intron	N/A	NP_001130002.1
	SERPINE2	NM_006216.4		c.488-1926C>T		intron	N/A	NP_006207.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SERPINE2	ENST00000409304.6	TSL:1 MANE Select	c.488-1926C>T		intron	N/A	ENSP00000386412.1
	SERPINE2	ENST00000258405.9	TSL:1	c.488-1926C>T		intron	N/A	ENSP00000258405.4
	SERPINE2	ENST00000409840.7	TSL:1	c.488-1926C>T		intron	N/A	ENSP00000386969.3

Frequencies

GnomAD3 genomes AF: 0.621 AC: 94394 AN: 151888 Hom.: 29754 Cov.: 32

Gnomad AFR AF: 0.543

Gnomad AMI AF: 0.604

Gnomad AMR AF: 0.714

Gnomad ASJ AF: 0.561

Gnomad EAS AF: 0.433

Gnomad SAS AF: 0.601

Gnomad FIN AF: 0.613

Gnomad MID AF: 0.617

Gnomad NFE AF: 0.668

Gnomad OTH AF: 0.632

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.621 AC: 94444 AN: 152006 Hom.: 29770 Cov.: 32 AF XY: 0.619 AC XY: 45993 AN XY: 74318

African (AFR) AF: 0.543 AC: 22494 AN: 41426

American (AMR) AF: 0.715 AC: 10929 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.561 AC: 1945 AN: 3464

East Asian (EAS) AF: 0.433 AC: 2239 AN: 5166

South Asian (SAS) AF: 0.602 AC: 2901 AN: 4822

European-Finnish (FIN) AF: 0.613 AC: 6479 AN: 10568

Middle Eastern (MID) AF: 0.609 AC: 179 AN: 294

European-Non Finnish (NFE) AF: 0.668 AC: 45408 AN: 67946

Other (OTH) AF: 0.625 AC: 1319 AN: 2112

Alfa AF: 0.640 Hom.: 6951

Bravo AF: 0.625

Asia WGS AF: 0.486 AC: 1690 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	9.2
DANN	Benign	0.68
PhyloP100		0.99
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: rs6721140; hg19: chr2-224858643;