chr2-224008887-G-A

Position:

• chr2-224008887-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_001136528.2(SERPINE2):​c.-22-6965C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0158 in 152,248 control chromosomes in the GnomAD database, including 35 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 0.016 (35 hom., cov: 33)
• Consequence: SERPINE2 NM_001136528.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.16

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]

LOC124907990 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0158 (2411/152248) while in subpopulation NFE AF= 0.0248 (1685/68020). AF 95% confidence interval is 0.0238. There are 35 homozygotes in gnomad4. There are 1137 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 2411 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SERPINE2	NM_001136528.2	c.-22-6965C>T		intron_variant		ENST00000409304.6	NP_001130000.1
LOC124907990	XR_007088102.1	n.11G>A		non_coding_transcript_exon_variant	1/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SERPINE2	ENST00000409304.6	c.-22-6965C>T		intron_variant		1	NM_001136528.2	ENSP00000386412	A1

Frequencies

GnomAD3 genomes AF: 0.0158 AC: 2411 AN: 152130 Hom.: 35 Cov.: 33

Gnomad AFR AF: 0.00430

Gnomad AMI AF: 0.105

Gnomad AMR AF: 0.0105

Gnomad ASJ AF: 0.00634

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00663

Gnomad FIN AF: 0.0166

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.0248

Gnomad OTH AF: 0.0268

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

GnomAD4 genome AF: 0.0158 AC: 2411 AN: 152248 Hom.: 35 Cov.: 33 AF XY: 0.0153 AC XY: 1137 AN XY: 74430

Gnomad4 AFR AF: 0.00428

Gnomad4 AMR AF: 0.0105

Gnomad4 ASJ AF: 0.00634

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00663

Gnomad4 FIN AF: 0.0166

Gnomad4 NFE AF: 0.0248

Gnomad4 OTH AF: 0.0265

Alfa AF: 0.0181 Hom.: 6

Bravo AF: 0.0159

Asia WGS AF: 0.00260 AC: 9 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.1
DANN	Benign	0.58

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

Publications

LitVar

Other links and lift over

dbSNP: rs7588220; hg19: chr2-224873604;